bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-Action Profiles of Novel Premixed Preparations of Insulin Lispro and NPL Insulin
Authors: Heise Tim , Weyer Christian , Serwas Andreas , Heinrichs Sebastian , Osinga Johannes , Roach Paris , Woodworth Jim , Gudat Uwe , Heinemann Lutz
Published: March 2007

OBJECTIVE

To study the pharmacodynamic properties of three premixed formulations of the rapid-acting insulin analog insulin lispro and its protamine-retarded preparation, neutral protamine lispro (NPL) insulin.

RESEARCH DESIGN AND METHODS

In this open, single-center, euglycemic glucose clamp study, 30 healthy volunteers (12 women, 18 men) aged 27 ± 2 years (mean ± SD), whose BM1 was 23.0 ± 2.3 kg/m2, received subcutaneous injections of 0.3 U/kg body wt of insulin mixture (high-mixture 75/25, mid-mixture 50/50, or low-mixture 25/75 insulin lispro/NPL insulin), insulin lispro, or NPL insulin on one of the five study days in randomized order. Glucose infusion rates were determined over a period of 24 h after administration.

RESULTS

Maximal metabolic activity decreased after subcutaneous injection of the mixtures with lower insulin lispro content; however, the time point of maximal and of early halfmaximal metabolic activity was comparable among the three mixtures. Higher proportions of insulin lispro resulted in higher values for area under the curve within the first 360 min after injection and a more rapid decline to late half-maximal activity. Serum insulin concentrations showed a similar pattern.

CONCLUSIONS

This study shows that the pharmacodynamic and pharmacokinetic properties of insulin lispro are preserved in stable mixtures with NPL insulin.
Beneficial Impact of Ramipril on Left Ventricular Hypertrophy in Normotensive Nonalbummuric NIDDM Patients
Authors: Nielsen Flemming S , Sato Asako , Ali Samir , Tarnow Lise , Smidt Ulla M , Kastrup Jens , Parving Hans-Henrik
Published: March 2007

OBJECTIVE

To evaluate the effect of the ACE inhibitor ramipril as compared with placebo on left ventricular mass index (LVMl) in normotensive, nonalbuminuric NIDDM patients with left ventricular hypertrophy (LVH). Patients with NIDDM are characterized by excessive cardiovascular morbidity and mortality, and LVH, an independent risk factor for cardiac events, is often present in NIDDM patients.

RESEARCH DESIGN AND METHODS

A total of 38normotensive, nonalbuminuric (albuminuria <100 mg/24 h) NIDDM patients with LVH (LVMl /131 g/m2in men and >100 g/m2 in women) were enrolled in a 6-month randomized, double-blind parallel group study to compare the effects of ramipril (5 mg/day) with placebo on LVMl (echocardiography, Vingmed CFM725, Diasonics Sonotron), QTC dispersion determined as the interlead variation in QTC interval on standard electrocardiogram (ECG), and 24-h ambulatory blood pressure (A&D TM2420, Tokyo, Japan). A total of 16 ramipril (10 men, 60 ± 9 years [mean ± SD]) and 15 placebo-treated (8 men, 55 ± 10 years) patients completed the study, and their data are presented.

RESULTS

Ambulatory blood pressure was almost identical at baseline (132/76 ± 3/1 vs. 133/74 ± 5/2 mmHg [mean ± SEM]) and remained stable during follow-up (134/76 ± 3/1 vs. 136/74 ± 6/2 mmHg) in the ramipril and placebo group, respectively. LVMl was comparable at baseline (137.1 ± 7.0 vs. 129.6 ± 3.7 g/m2) in the ramipril and placebo group, respectively, and decreased significantly more in the ramipril group as compared with the placebo group (17.6 ± 3.0 vs. 5.7 ± 4.6 g/m2, respectively, 11.9 [0.7–23.1] g/m2, mean difference [95% CI]; P = 0.037). QTC dispersion was comparable at baseline (60.2 [5.5] vs. 64.1 [6.5] ms) and did not change significantly during follow-up: −2.5 [7.0] vs. −12.2 [9.5] ms; mean difference 9.8 (−14.2 to 33.8 ms) in the ramipril and placebo group, respectively.

CONCLUSIONS

Ramipril induces regression of LVH in normotensive, nonalbuminuric NIDDM patients, independent of reduction in systemic blood pressure.
Efficacy and Safely of a Topical Gel Formulation of Recombinant Human Platelet-Derived Growth Factor-BB (Becaplermin) in Patients With Chronic Neuropathic Diabetic Ulcers: A phase III randomized placebo-controlled double-blind study
Authors: Wieman T Jeffery , Smiell Janice M , Su Yachin
Published: March 2007

OBJECTIVE

To compare the efficacy and safety of topically applied recombinant human platelet-derived growth factor-BB (rhPDGF-BB) (becaplermin) with placebo gel in patients with chronic diabetic neuropathic ulcers of the lower extremities.

RESEARCH DESIGN AND METHODS

This multicenter double-blind placebo-controlled phase 111 trial included 382 patients with type 1 or type 2 diabetes and chronic ulcers of at least 8 weeks' duration. After sharp debridement of the ulcer, patients were randomized to receive becaplermin gel 30 μg/g, becaplermin gel 100 μg/g, or placebo gel, in conjunction with a standardized regimen of good wound care until complete wound closure was achieved or for a maximum of 20 weeks. Moist saline-soaked gauze dressings were changed twice daily with study medication applied by patients or caregivers at the evening dressing change. Safety was assessed by monitoring adverse events (AEs) and by clinical laboratory evaluations.

RESULTS

Compared with placebo gel, becaplermin gel 100 μg/g significantly increased the incidence of complete wound closure by 43% (50 vs. 35%, P = 0.007) and decreased the time to achieve complete wound closure by 32% (86 vs. 127 days; estimated 35th percentile, P = 0.013). AEs reported during treatment or during a 3-month follow-up period were similar in nature and incidence across all treatment groups.

CONCLUSIONS

Becaplermin gel 100 μg/g, in conjunction with good wound care, significantly increased the incidence of complete wound closure and significantly reduced the time to complete closure of chronic diabetic neuropathic ulcers. The safety profile of becaplermin gel was similar to that of placebo gel.
Evaluation of the Insertion/Deletion ACE Gene Polymorphism as a Risk Factor for Carotid Artery Intima-Media Thickening and Hypertension in Young Type 1 Diabetic Patients
Authors: Frost Dietmar , Pfohl Martin , Clemens Pia , Haring Hans-Ulrich , Beischer Wolfgang
Published: March 2007

OBJECTIVE

To study the distribution of the insertion/deletion polymorphism of the ACE gene in young type 1 diabetic patients and to evaluate possible associations between the ACE genotype, arterial hypertension, and intima-media thickness (IMT) of the common carotid artery.

RESEARCH DESIGN AND METHODS

Study participants were 148 type 1 diabetic patients (56 men and 92 women), aged 14–44 years, with a diabetes duration of ≥2 years. HbA1c, albuminuria, and lipid status were assessed by standard laboratory techniques; the ACE genotypes were assessed by polymerase chain reaction. The patients were categorized according to the presence or absence of hypertension, nephropathy, and retinopathy. The IMT, which can be used to estimate early stages of atherosclerosis, was measured by high-resolution ultrasonography.

RESULTS

The ACE genotypes were distributed as follows: 21% II, 37% ID, 42% DD. The IMT values did not differ among patients with various ACE genotypes (0.63 ± 0.15 mm), but the prevalence of hypertension was significantly higher in patients with DD (odds ratio, 4.26 versus II ± ID; 95% CI, 1.64–11.06). Multiple linear regression analysis showed that only age, hypertension, and sex were determinants for the IMT.

CONCLUSIONS

Our results suggest a relationship between the prevalence of hypertension and the deletion polymorphism of the ACE gene in young type 1 diabetic patients, but we could not find an association between carotid artery IMT and ACE genotype in this population.
Impact of a Diabetes Electronic Management System on the Care of Patients Seen in a Subspecialty Diabetes Clinic
Authors: Smith Steven A , Murphy Mary E , Huschka Todd R , Dinneen Sean F , Gorman Colum A , Zimmerman Bruce R , Rizza Robert A , Naessens James M
Published: March 2007

OBJECTIVE

To compare the compliance with diabetes care performance indicators by diabetes specialists using a diabetes electronic management system (DEMS) and by those using the traditional paper medical record.

RESEARCH DESIGN AND METHODS

A DEMS has been gradually introduced into our subspecialty practice for diabetes care. To assess the value of this DEMS as a disease management tool, we completed a retrospective review of the medical records of 82 randomly selected patients attending a subspecialty diabetes clinic (DC) during the first quarter of 1996. Eligible patients were defined by the suggested criteria from the American Diabetes Association Provider Recognition Program. During the first quarter of 1996, ∼ one half of the providers began using the DEMS for some but not all of their patient encounters. Neither abstractors nor providers were aware of the intent to examine performance in relationship to use of the DEMS.

RESULTS

Several measures were positively influenced when providers used the DEMS. The number of foot examinations, the number of blood pressure readings, and a weighted criterion score were greater (P < 0.01) for providers using the DEMS. There was evidence, although not statistically significant, for lower mean diastolic blood pressures (P = 0.043) in patients and for number of glycated hemoglobins documented (P = 0.018) by users of the DEMS.

CONCLUSIONS

Performance and documentation of the process of care for patients with diabetes in a subspecialty clinic are greater with the use of a DEMS than with the traditional paper record.
Comorbidity of Diabetes and Eating Disorders: Does diabetes control reflect disturbed eating behavior?
Authors: Herpertz Stephan , Albus Christian , Wagener Ruth , Kocnar Margit , Wagner Richard , Henning Andreas , Best Frank , Foerster Helmut , Schleppinghoff Bernd Schulze , Thomas Walter , Köhle Karl , Mann Klaus , Senf Wolfgang
Published: March 2007

OBJECTIVE

This multicenter study was designed to explore the prevalence of clinical and subclinical eating disorders (EDs), the extent of intentional omission of insulin and oral antidiabetic agents, and its relationship to glycemic control in an inpatient and outpatient population of men and women with type 1 and type 2 diabetes.

RESEARCH DESIGN AND METHODS

Data have been collected from 12 diabetes medical centers in two German cities. In a questionnaire and interview-based study, a sample of male and female patients (n = 341 type 1, n = 322 type 2) was assessed for the following eating disorders: anorexia nervosa, bulimia nervosa, binge eating disorder, and eating disorder not otherwise specified. For lack of interview data of several patients meeting the screening criteria, prevalence ranges were calculated.

RESULTS

The overall prevalence range of current EDs was 5.9–8.0% (lifetime prevalence 10.3–14.0%). When patients were stratified according to type 1 and type 2 diabetes, there was no difference in prevalence of EDs. However, the distribution of the EDs was different in both types of diabetes, with a predominance of binge eating disorder in the type 2 diabetes sample. Type 1 (5.9%) and type 2 (2.2%) diabetic patients reported deliberate omission of hyperglycemic drugs (insulin or oral agents) in order to lose weight. Compared with control subjects, neither the presence of EDs nor insulin omission influenced diabetic control.

CONCLUSIONS

There seems to be no difference in prevalence rates of EDs in both types of diabetes; however, distribution of EDs is different. The findings suggest that neither EDs nor insulin omission are necessarily associated with poor control of glycemia. Binge eating disorder seems to precede type 2 diabetes in most patients and could be one of the causes of obesity that often precedes type 2 diabetes.
Power Spectral Analysis of Heart Rate Variation in Diabetic Patients With Neuropathic Foot Ulceration
Authors: Aso Yoshimasa , Fujiwara Yukio , Inukai Toshihiko , Takemura Yoshihiro
Published: March 2007

OBJECTIVE

To evaluate the relationship between diabetic autonomic neuropathy and diabetic neuropathic foot ulceration, we used power spectral analysis (PSA) of heart rate variation, which provides the accurate simultaneous quantification of parasympathetic and sympathetic activities, to assess autonomic function in diabetic patients.

RESEARCH DESIGN AND METHODS

We studied 55 NIDDM patients including 10 diabetic patients without neuropathy, 23 diabetic patients with neuropathy and no history of foot ulceration, and 22 diabetic patients with neuropathic foot ulceration. We performed PSA of 100 R-R intervals at rest and analyzed the results by fast Fourier transformation.

RESULTS

The low frequency (LF) power, which reflects sympathetic activity, and the high frequency (HF) power, which reflects parasympathetic (vagal) activity, were inversely correlated with the duration of diabetes and the fasting plasma glucose (FPG) levels. By multiple regression analysis, the FPG remained with significant influence on both LF and HF powers. The LF and HF powers were positively correlated with motor nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) in the upper and lower limbs and the coefficient of variation of R-R intervals. The LF and HF powers were significantly reduced in patients with neuropathy and patients with foot ulceration compared with patients without neuropathy. Although the median MCV and SCV were similar between diabetic patients with neuropathy and patients with foot ulceration, both the LF and HF powers were significantly decreased in patients with foot ulceration compared with patients with neuropathy. There was no difference in the value of the LF:HF ratio, an index of sympathovagal balance, among three subgroups. We observed a positive correlation between LF and HF power in all subjects; however, the LF and HF powers were not correlated in the subgroups of patients with foot ulceration.

CONCLUSIONS

These results showed that diabetic patients with neuropathic foot ulceration have a greater impairment in spectral indexes of autonomic activity obtained by PSA than patients with neuropathy and no history of foot ulceration, whereas no difference was present in nerve conduction velocities.
Progression to Type 2 Diabetes Among Hign-Risk Groups in Kin-Chen, Kinmen: Exploring the natural history of type 2 diabetes
Authors: Chou Pesus , Li Chia-Lin , Wu Gin-Son , Tsai Shih-Tzer
Published: March 2007

OBJECTIVE

To examine the natural history of 654 high-risk subjects (340 men and 314 women) with fasting hyperglycemia (first fasting plasma glucose [FPG] level 5.6–7.8 mmol/1) who also exhibited 2-h postload glucose concentrations <11.1 mmol/1 and an FPG level <7.8 mmol/1 in a 75-g oral glucose tolerance test (OGTT). We were particularly interested in comparing the likelihood of developing type 2 diabetes for those with persistent fasting hyperglycemia (PFH), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). PFH is a relatively new definition, and those with PFH used to be defined as NGT according to WHO criteria.

RESEARCH DESIGN AND METHODS

Subjects were located in a 1992–1994 community-based population survey and followed up and reexamined during 1995–1996. An OGTT was used to determine who had progressed to type 2 diabetes. Risk factors predictive of subsequent progression to type 2 diabetes were determined by comparing baseline variables from the 1992–1994 survey with data of those who had or had not progressed to type 2 diabetes in 1995–1996.

RESULTS

Of 654 high-risk subjects screened in the baseline survey 481 (73.5%, 255 men and 226 women) were followed up. Of these, 8.1% had progressed to diabetes (4.1% progression/year, 95% Cl 2.3–5.9). Of 131 baseline IGT subjects, 17.6% progressed to diabetes (8.8% progression/year, 6.3–11.3), but only 7.4% of 95 PFH subjects (3.7% progression/year, 2.0–5.4) and 3.5% of 255 NGT subjects (1.8% progression/year, 0.1–3.0) progressed to diabetes.

CONCLUSIONS

The rates of progression to type 2 diabetes were lowest from the NGT subgroup, highest from the IGT group, with the PFH group in the middle, suggesting that PFH might be a transitional condition that precedes IGT and diabetes. Other significant predictors of subsequent diabetes were baseline BMI, baseline hyperuricemia, baseline FPG, and 2-h plasma glucose concentration.
Troglitazone Reduces Plasma Leptin Concentration but Increases Hunger in NIDDM Patients
Authors: Shimizu Hiroyuki , Tsuchiya Takahumi , Sato Noriyuki , Shimomura Yohnosuke , Kobayashi Isao , Mori Masatomo
Published: March 2007

OBJECTIVE

Troglitazone, which improves peripheral insulin resistance of experimental diabetic animals and diabetic patients, affects ob gene expression in the adipose tissue of rodents. The present study was undertaken to examine a hypothesis that clinical administration of troglitazone may reduce circulating leptin levels and affect eating behavior in NIDDM patients.

RESEARCH DESIGN AND METHODS

Troglitazone was administered at a dosage of 200 mg twice daily for 12 weeks in 20 poorly controlled NIDDM patients. Chronological changes in glycemic control, serum lipids, immunoreactive leptin (IRL) levels, and BMI were measured. Body fat weight was also assessed by bioelectric impedance.

RESULTS

Troglitazone significantly decreased fasting plasma glucose, serum immunoreactive insulin, and HbA1c levels. Serum levels of IRL and triglyceride were significantly reduced by troglitazone administered for 4, 8, and 12 weeks. Troglitazone administration significantly increased the BMI in NIDDM patients, and two-thirds of the patients complained of increased hunger after the start of troglitazone administration.

CONCLUSIONS

Troglitazone significantly reduces circulating leptin levels at clinical doses. It may affect the eating behavior of poorly controlled NIDDM patients through the improvement of glycemic control and/or the reduction of circulating leptin.
Comparison of Percent Total GHb With Percent HbA1c in People With and Without Known Diabetes
Authors: Nuttall Frank Q
Published: March 2007

OBJECTIVE

To directly compare results obtained using an ion-exchange high-performance liquid chromatography (HPLC) HbA1c method used in the Diabetes Control and Complications Trial with two different affinity chromatography methods in which ”total GHb” is determined.

RESEARCH DESIGN AND METHODS

Blood was obtained from a large number of people with and without known diabetes. The specimens were divided and assayed for HbA1c and for total GHb. Total GHb was determined using a semi-automated gravity-elution boronate affinity chromatography method and an automated boronate affinity HPLC method. The results obtained with the two methods were also compared.

RESULTS

In subjects without known diabetes, the mean percentage HbA1c and the range of values were similar to the total GHb values in the same subjects when assayed using the semi-automated affinity gravity-elution method (mean 5.2 ± 0.4 and 5.1 ± 0.4% [SD], respectively). With the affinity HPLC method, results were 5.3 ± 0.4%. The similarity in results was surprising. However, analysis of the data suggests that a large proportion of the material in the HbA1c fraction measured using this ion-exchange HPLC method is not GHb, as pointed out by others. Although the results were similar in people without known diabetes, in the people with diabetes, the incremental increase was ∼25% greater for the total GHb when compared with the increase in HbA1c. When corrected for the non-GHb being measured by the HbA1c method, it can be calculated that ∼40% more GHb is measured using affinity chromatography over the entire range of GHb values.

CONCLUSIONS

The similarity in the mean and range of percent HbA1c and in percent total GHb using these different methods can be attributed to two factors: 1) the HbA1c ion-exchange method measures only ∼ 50–60% of the total GHb present, and 2) ∼ 40–50% of the material being measured in the HbA1c fraction is not GHb, i.e., offsetting factors fortuitously resulted in values similar to the more specific affinity methods. The greater incremental increase in percent total GHb compared with percent HbA1c in people with diabetes can be attributed to the greater amount of GHb being measured with the affinity methods.
Irreversibility of the Defect in Glycogen Synthase Activity in Skeletal Muscle From Obese Patients With NIDDM Treated With Diet and Metformin
Authors: Damsbo Peter , Hermann Leif S , Vaag Allan , Hother-Nielsen Ole , Beck-Nielsen Henning
Published: March 2007

OBJECTIVE

To assess the reversibility of the defect in glycogen synthase (GS) activity in skeletal muscle from obese patients with NIDDM treated with a hypocaloric diet and metformin.

RESEARCH DESIGN AND METHODS

Eighteen obese patients newly diagnosed with NIDDM were included in a randomized placebo-controlled double-blind parallel group trial and followed for 3 months. Euglycemic-hyperinsulinemic clamp including indirect calorimetry and biopsy of m. vastus lateralis was performed before and after treatment with a hypocaloric diet plus metformin or placebo. The patients were studied at basal, low, and high insulin concentrations.

RESULTS

The impaired GS activity in muscle biopsies was not reversed either by acute normalization of glycemia (for 8 h) or by chronic reduction of hyperglycemia by diet plus metformin. In both treatment groups, comparable effects on glycemic control and weight loss were found together with marked insulin suppression of nonesterified fatty acids and increased glucose oxidation. Total glucose disposal at euglycemic-hyperinsulinemic clamp increased significantly in the metformin group by 25% at high insulin level (259 ± 31 vs. 207 ± 21 mg · m−2 · min−1, P < 0.05). An insignificant increase by 13% was found in the placebo group. There were no significant changes in nonoxidative glucose metabolism. GS activity and glucose utilization showed no significant differences between the two treatment groups when regression coefficients, expressed as incremental changes by increments of insulin, were compared.

CONCLUSIONS

Defective GS activity in obese NIDDM patients is not secondary to hyperglycemia. Metformin and diet had no significant influence on GS activity. The added effect of metformin to that of a hypocaloric diet in improving insulin-stimulated glucose utilization is marginal when blood glucose reduction is obtained by weight loss.
Urinary Albumin Excretion Rate and Glomerular Filtration Rate in Single-Kidney Type 2 Diabetic Patients
Authors: Silveiro Sandra P , da Costa Luciana A , Beck Maristela O , Gross Jorge L
Published: March 2007

OBJECTIVE

To evaluate the urinary albumin excretion rate (UAER) and the glomerular filtration rate (GFR) of single-kidney type 2 diabetic patients (SKD) and of single-kidney non-diabetic patients (SKN).

RESEARCH DESIGN AND METHODS

Patients who had only one kidney for at least 5 years, with no renal disease or hypertension at the time of the nephrectomy and with no calculus or systemic disease at the time of the evaluation, were included in this controlled cross-sectional study A total of 20 SKD (8 men, age 62 ± 9 years; diabetes duration 8.5 ± 7 years), 17 SKN (2 men, age 57 ± 13 years), and 184 type 2 diabetic patients who were matched to the single-kidney diabetic group for age, sex, and BMI were studied. UAER was measured by immunoturbidimetry in timed 24-h sterile urine, and GFR was determined by the 51Cr-EDTA single-injection method.

RESULTS

SKD patients presented a higher proportion (8 of 20, 40%) of microalbuminuria (UAER 20-200 μg/min) than SKN patients (3 of 17, 17.6%) and type 2 diabetic patients (37 of 184, 20%). SKD patients presented a higher proportion of macroalbuminuria (UAER >200 μg/min; 6 of 20, 30%) than SKN patients (1 of 17, 6%) but were similar to type 2 diabetic patients (43 of 184, 23%). The GFRs of normoalbuminuric SKN (71.7 ± 21.4 ml · min−1 · 1.73 m−2) and SKD patients (73.0 ± 21.5 ml · min−1 · 1.73 m−2) were similar but higher than the one-kidney GFR (GFR ÷ 2) of the age-, sex-, and BMI-matched normal individuals (50.5 ± 9.0 ml · min−1 · 1.73 m−2) and normoalbuminuric type 2 diabetic patients (54.0 ± 11.6 ml · min−1 · 1.73 m−2).

CONCLUSIONS

Increased GFR related to single-kidney status confers an increased risk of developing renal disease in the presence of diabetes.
Interaction of sulfonylureas and exercise on glucose homeostasis in type 2 diabetic patients.
Authors: Larsen J J , Dela F , Madsbad S , Vibe-Petersen J , Galbo H
Published: March 2007

OBJECTIVE: To determine whether the plasma glucose-lowering effects of sulfonylureas and acute submaximal exercise are additive and, accordingly, to determine whether they may increase the risk of hypoglycemia when combined in fasting patients. RESEARCH DESIGN AND METHODS: Eight postabsorptive type 2 diabetic patients were examined at three occasions: after oral sulfonylurea (7 mg glibenclamide), during 60 min of ergometer cycle exercise at 57 +/- 3% of VO2max, and during exercise after glibenclamide. RESULTS: Heart rate, VO2, and lactate responses to exercise were comparable (P > 0.05) on days with and without glibenclamide. Plasma insulin concentrations were always increased by glibenclamide, and they were lowered identically by exercise with and without glibenclamide. However, throughout exercise, absolute concentrations of insulin were lower on days without glibenclamide compared with days with glibenclamide (34.5 +/- 4.7 vs. 47.4 +/- 5.5 pmol/l; P < 0.05). At the start of exercise, glucose concentrations were similar between experiments (P > 0.05). The rate of decrease in glucose during exercise was higher (P < 0.05) on days with both glibenclamide and exercise, compared with days with glibenclamide alone and days with exercise alone (-0.035 +/- 0.009 vs. -0.016 +/- 0.002 and -0.022 +/- 0.005 mmol.l-1.min-1, respectively). Consequently, the glucose nadir was lower on days with glibenclamide and exercise than on days with glibenclamide or exercise alone (6.7 +/- 1.1 vs. 8.1 +/- 0.9 and 7.6 +/- 1.0 mmol/l, respectively; P < 0.05). During exercise, the rate of appearance of plasma glucose determined by 3-[3H]glucose infusion was lower on days with glibenclamide than on days without glibenclamide (2.3 +/- 0.1 vs. 2.9 +/- 0.1 mg.min-1.kg-1; P < 0.05). In contrast, glucose clearance was identical (P > 0.05). CONCLUSIONS: In postabsorptive type 2 diabetic patients, the hypoglycemic action of glibenclamide and exercise is enhanced when the treatments are combined. The interaction reflects an increased inhibition by glibenclamide-enhanced insulin levels of hepatic glucose production when hepatic glucose production is accelerated by exercise.
Specific fiber deficits in sensorimotor diabetic polyneuropathy correspond to cytotoxicity against neuroblastoma cells of sera from patients with diabetes.
Authors: Pittenger G L , Malik R A , Burcus N , Boulton A J , Vinik A I
Published: March 2007

OBJECTIVE: Neuropathy is the most common complication of diabetes, and toxic serum factors may contribute to its genesis. RESEARCH DESIGN AND METHODS: We assessed neurotoxicity in the serum of 39 diabetic patients and correlated it with clinical measures of somatic and autonomic nerve fiber damage. Sera were applied to N1E-115 and VSC4.1 neuroblastoma cells in vitro as models of sensory/autonomic (S/A) and motor neurons, respectively. Neurotoxicity was measured as either complete or near-complete cell death (highly toxic), inhibited cell growth (moderately toxic), or normal cell proliferation (nontoxic) compared with pooled human serum controls during culture over 4 days. RESULTS: There was an inverse correlation between neurotoxicity and vibration perception threshold (P < 0.01). Age (P < 0.02), duration of diabetes (P < 0.02), and HbA1c (P < 0.03) correlated with neurotoxicity, suggesting that glycation may contribute to cytotoxicity in this model. S/A neurotoxicity occurred more frequently in the sera of patients with type 1 (19 of 25) than type 2 (5 of 14) diabetes (P < 0.02). None of the sera from either type 1 or type 2 diabetic patients displayed neurotoxicity on VSC4.1 cells, whereas sera from patients with motor neuropathy were highly toxic. CONCLUSIONS: These studies indicate that there is a relationship between the specific nerve fiber dysfunction in the patient and the type of neuronal cell killed, not only for diabetic neuropathy but also for known forms of autoimmune neuropathies. Such toxic factors may contribute to diabetic neuropathy by acting in concert with hyperglycemia to damage sensory/autonomic neurons.
Diabetes and serum ferritin concentration among U.S. adults.
Authors: Ford E S , Cogswell M E
Published: March 2007

OBJECTIVE: We examined the association between serum ferritin concentration and the risk of diabetes. RESEARCH DESIGN AND METHODS: We examined the cross-sectional associations among ferritin concentration, glucose tolerance status, and concentrations of insulin, glucose, and glycosylated hemoglobin in 9,486 U.S. adults aged > or = 20 years from the Third National Health and Nutrition Examination Survey (1988-1994). RESULTS: After adjusting for age, sex, ethnicity, education, BMI, alcohol consumption, alanine aminotransferase concentration, C-reactive protein concentration, and examination session attended, and after dichotomizing ferritin concentration into < 300 and > or = 300 micrograms/l for men and < 150 and > or = 150 micrograms/l for women, the odds ratios for newly diagnosed diabetes were 4.94 (95% CI 3.05-8.01) for men and 3.61 (2.01-6.48) for women. The increased risk of newly diagnosed diabetes was concentrated among participants with transferrin saturations < 45%. All multiple linear regression coefficients between ferritin concentration and concentrations of insulin, glucose, and glycosylated hemoglobin were positive and significant for both men and women. CONCLUSIONS: Elevated serum ferritin concentration was associated with an increased risk of diabetes. We were unable to eliminate conclusively the possibility that the observed association reflected inflammation rather than excess body iron stores.
Low-dose ethanol predisposes elderly fasted patients with type 2 diabetes to sulfonylurea-induced low blood glucose.
Authors: Burge M R , Zeise T M , Sobhy T A , Rassam A G , Schade D S
Published: March 2007

OBJECTIVE: It has previously been demonstrated that the risk of hypoglycemia is low among otherwise healthy elderly fasted patients with type 2 diabetes taking oral sulfonylurea medications. Nevertheless, these agents do cause hypoglycemia in clinical practice, suggesting that accompanying factors must typically be present for hypoglycemia to occur. Ethanol is one putative risk factor that has not been evaluated as a mechanism for low blood glucose among sulfonylurea users. We hypothesized that low concentrations of ethanol would reduce blood glucose concentrations in elderly type 2 diabetic patients receiving sulfonylureas during a short-term fast. RESEARCH DESIGN AND METHODS: A total of 10 type 2 diabetic patients, aged 68 +/- 3 years and receiving 20 mg glyburide daily, participated in a prospective double-blind placebo-controlled in-patient study consisting of two 24-h fasts at least 1 week apart. During hours 14 and 15 of the fasting studies, subjects received intravenous infusions of either 4.35 mmol.kg-1.h-1 ethanol (equivalent to one or two alcoholic beverages) or saline placebo in random order. Ethanol, plasma glucose, insulin, and counterregulatory hormones were assessed very 30-60 min during the final 10 h of the fast. RESULTS: Blood ethanol levels peaked at 17 +/- 2 mmol/l (the lower legal limit of intoxication in New Mexico) during the ethanol study. Plasma glucose concentrations did not differ at baseline (placebo 8.5 +/- 1.8 vs. ethanol 8.7 +/- 1.7 mmol/l; P = 0.50), but nadir plasma glucose was lower after the ethanol infusion compared with placebo (4.4 +/- 1.2 vs. 5.0 +/- 1.4 mmol/l; P = 0.01), and the absolute decline in plasma glucose was also greater during the ethanol study than the placebo study (4.7 +/- 0.9 vs. 3.6 +/- 1.2 mmol/l; P = 0.01). Counterregulatory hormone levels were increased during the ethanol study and nonesterified fatty acid concentrations were suppressed compared with the placebo study. CONCLUSIONS: Low doses of ethanol predispose fasted elderly type 2 diabetic patients to low blood glucose during a short-term fast. This may be one of several mechanisms by which sulfonylurea-induced hypoglycemia occurs in elderly patients.
In vivo endothelial dysfunction characterizes patients with impaired fasting glucose.
Authors: Vehkavaara S , Seppälä-Lindroos A , Westerbacka J , Groop P H , Yki-Järvinen H
Published: March 2007

OBJECTIVE: The American Diabetes Association has recently defined a new category of abnormal glucose homeostasis called "impaired fasting glucose" (IFG), where glucose levels do not meet the criteria of diabetes but are too high to be considered normal. We determined whether endothelial dysfunction is a characteristic of subjects with IFG. RESEARCH DESIGN AND METHODS: In vivo vasodilatory responses to intra-arterial infusions of endothelium-dependent (acetylcholine [ACh]) and -independent (sodium nitroprusside [SNP]) vasoactive agents were determined in 17 IFG subjects (age 63 +/- 1 years, BMI 26.5 +/- 0.8 kg/m2, serum LDL cholesterol 3.5 +/- 0.2 mmol/l) with fasting plasma glucose levels of 117 +/- 1 mg/dl and in 12 subjects with normal fasting plasma glucose concentrations. RESULTS: The blood-flow response to the low dose of ACh was 46% (5.9 +/- 0.7 vs. 10.9 +/- 1.3 ml.dl-1.min-1, IFG vs. normal, P < 0.01) and to the high dose was 31% (9.1 +/- 1.2 vs. 13.2 +/- 1.5 ml.dl-1.min-1, P < 0.05, respectively) lower in the IFG than in the normal subjects. In contrast, blood-flow responses to both low (7.8 +/- 0.5 vs. 9.0 +/- 0.9 ml.dl-1.min-1, IFG vs. normal, NS) and high (11.6 +/- 1.2 vs. 12.3 +/- 1.3 ml.dl-1.min-1, NS, respectively) doses of SNP were comparable. The ratio of endothelium-dependent to -independent blood flow was 40% lower in the IFG (0.75 +/- 0.1) than in the normal (1.24 +/- 0.1, P < 0.001) subjects. Both fasting plasma glucose (r = -0.48, P < 0.01) and glycosylated hemoglobin (r = -0.42, P < 0.05) were inversely correlated with endothelium-dependent vasodilation but not with other parameters, such as weight, blood pressure, or lipids. CONCLUSIONS: We conclude that vascular dysfunction is associated with abnormal, although nondiabetic, glucose homeostasis.
Walking training for intermittent claudication in diabetes.
Authors: Ubels F L , Links T P , Sluiter W J , Reitsma W D , Smit A J
Published: March 2007

OBJECTIVE: Walking training (WT) is an established treatment for patients with intermittent claudication (IC). Abnormalities specific to diabetes, such as a relative preponderance of distal lesions and the contribution of microcirculatory disease, might well influence the results of WT. We compared changes in walking distance during WT in diabetic patients with those in nondiabetic control subjects. RESEARCH DESIGN AND METHODS: In consecutive patients with limiting IC and proven peripheral vascular disease, 33 patients with diabetes were compared with 136 control subjects during a half-year supervised WT program. Walking parameters were determined every 2 months, while vascular parameters were obtained at the start and end of the program. RESULTS: Of the 33 diabetic patients, 25 (76%) completed the program, as did 87 of the 136 (64%) control subjects. Thereafter, the symptom-free walking distance and the maximum walking distance (MWD) were significantly increased in diabetic patients from 142 +/- 30 to 339 +/- 57 m and from 266 +/- 39 to 603 +/- 52 m, respectively, and in control subjects from 126 +/- 8 to 400 +/- 39 m and from 292 +/- 18 to 628 +/- 36 m, respectively. The relative gain in MWD was 88% greater in those with diabetes. The vascular parameters were comparable for both groups before and after WT. CONCLUSIONS: WT is an effective treatment for IC, with a greater relative gain in diabetic patients.
Severity of glomerulopathy predicts long-term urinary albumin excretion rate in patients with type 1 diabetes and microalbuminuria.
Authors: Bangstad H J , Osterby R , Hartmann A , Berg T J , Hanssen K F
Published: March 2007

OBJECTIVE: To investigate whether the degree of glomerular structural lesions in young patients with type 1 diabetes and microalbuminuria was associated with urinary albumin excretion rate (AER) 6 years later and whether the AER level was influenced by blood glucose control, blood pressure, or glomerular filtration rate (GFR). RESEARCH DESIGN AND METHODS: There were 17 young adults with type 1 diabetes and microalbuminuria, 8 men and 9 women with mean age 20 years (95% CI: 18-22) and duration of diabetes of 11 years (10-13), who participated in a 6-year prospective study. Kidney biopsies (measurements of basement membrane thickness [BMT] and mesangial and matrix volume fractions) and GFR were performed at baseline. AER and HbA1c were measured at least three times a year and blood pressure once a year. RESULTS: In a multivariate analysis, baseline BMT and mean 6-year HbA1c contributed significantly to AER at the end of the study (R2 = 0.69, P < 0.01). When mesangial volume fraction replaced BMT as the independent variable, this parameter and AER at baseline predicted the AER at 6 years (R2 = 0.55, P < 0.55). Mesangial volume fraction and BMT (in separate analysis) contributed significantly to change in AER during the study. During the study, neither AER (30 micrograms/min [19-40] to 16 micrograms/min [7-90]) nor blood pressure (96 mmHg [92-102] to 95 mmHg [91-98]) changed significantly in the group. However, HbA1c was reduced from 10.3 (9.6-11.0) to 8.4% (7.8-9.1) (P < 0.01). CONCLUSIONS: In young patients with microalbuminuria, the long-term urinary AER was predicted by the degree of glomerular structural changes and associated with blood glucose control, but not with blood pressure or GFR.
Relationships of fasting and postload glucose levels to sex and alcohol consumption. Are American Diabetes Association criteria biased against detection of diabetes in women?
Authors: Pomerleau J , McKeigue P M , Chaturvedi N
Published: March 2007

OBJECTIVE: To compare, in men and women, the prevalence of undiagnosed type 2 diabetes assessed using criteria from the American Diabetes Association (ADA) and the World Health Organization (WHO) and to investigate risk factors associated with fasting and 2-h postload plasma glucose. RESEARCH DESIGN AND METHODS: Data from two companion surveys of Europeans, South Asians, and Afro-Caribbeans in west London were used. A total of 4,367 men and women aged 40-64 years who were not known to have diabetes underwent an oral glucose tolerance test after an overnight fast. The prevalence of undiagnosed diabetes was estimated using the ADA (fasting plasma glucose > or = 7.0 mmol/l) and WHO (2-h postload glucose > or = 11.1 mmol/l) criteria for epidemiologic studies. The association of body fat and usual alcohol intake with plasma glucose and diabetes prevalence was assessed. RESULTS: Compared with the WHO criterion, the ADA criterion gave a higher prevalence of diabetes in men (6.4 vs. 4.7%) but a lower prevalence in women (3.3 vs. 4.2%). In Afro-Caribbeans, the sex difference in diabetes prevalence was reversed. Women had significantly lower fasting glucose than men despite higher 2-h glucose levels. Alcohol intake was positively associated with fasting glucose in men and women but not with 2-h glucose levels. CONCLUSIONS: The new ADA criterion, based on fasting glucose alone, does not take account of sex differences in metabolic response to fasting or possible artifactual effects on fasting glucose. With the ADA criterion, alcohol intake was a significant risk factor for diabetes in our study population; this was not the case with the WHO criterion.
Effect of moderate improvement in metabolic control on magnesium and lipid concentrations in patients with type 1 diabetes.
Authors: Djurhuus M S , Henriksen J E , Klitgaard N A , Blaabjerg O , Thye-Rønn P , Altura B M , Altura B T , Beck-Nielsen H
Published: March 2007

OBJECTIVE: To evaluate the effect of clinically obtainable improvements in metabolic control in patients with type 1 diabetes on biochemical cardiovascular risk factors. RESEARCH DESIGN AND METHODS: Blood and 24-h urinary samples were obtained from 49 patients with type 1 diabetes before and after a run-in period and after 3 months of intervention, with frequent adjustment of insulin dosage according to measured blood glucose concentrations. RESULTS: The intervention caused a mean insulin dosage increment of 10%, a 20% decrease in fasting plasma glucose concentration, a 10% decrease in albumin corrected serum fructosamine, and a somewhat lesser decrease in HbAlc.A 14% decrease in the renal excretion of magnesium (Mg) was observed, but without a change in average serum Mg concentration. Serum HDL cholesterol increased 4%, and serum triglycerides decreased 10% as an average. Looking at individual patients, the decrease in serum triglycerides correlated with both the change in serum total Mg concentration and with the increase in insulin dosage. Using the change in serum total Mg concentration and in insulin dosage as independent variables in a multiple regression analysis, the coefficient of correlation with the decrease in serum triglycerides was 0.52. CONCLUSIONS: Moderate but clinically obtainable improvement of metabolic control in patients with type 1 diabetes seems to reduce the loss of Mg, increase serum HDL cholesterol, and decrease serum triglycerides. The decrease in serum triglycerides was associated with the change in serum total Mg concentration. These reductions in Mg loss and serum triglycerides might reduce the risk of developing cardiovascular disease in patients with type 1 diabetes.
Effectiveness of human ultralente versus NPH insulin in providing basal insulin replacement for an insulin lispro multiple daily injection regimen. A double-blind randomized prospective trial. The Canadian Lispro Study Group.
Authors: Zinman B , Ross S , Campos R V , Strack T
Published: March 2007

OBJECTIVE: To compare human ultralente (UL) insulin with human NPH insulin as basal insulin replacement in patients who use insulin lispro before meals. RESEARCH DESIGN AND METHODS: There were 178 patients with type 1 diabetes who were randomized to receive either human NPH or UL insulin once daily at bedtime in a 1-year double-blind clinical study. Eight-point blood glucose profiles were collected once monthly in the first 4 months, then every 2 months for the remainder of the study. Patients were also asked to perform premeal blood glucose measurements every day throughout the study. If before-supper blood glucose levels consistently exceeded 8 mmol/l despite optimal postprandial control with the lunch dose of insulin lispro, a second dose of basal insulin before breakfast was administered. RESULTS: For the group as a whole, insulin doses before meals and basal insulin doses were similar at baseline. At study's end, meal doses remained the same (30 +/- 1 U/day for UL., 29 +/- 1 U/day for NPH), while basal requirements were somewhat higher for the UL group than the NPH group: 30 +/- 1 U/day vs. 26 +/- 1 U/day, respectively (P < 0.05). The rates of severe hypoglycemia were similar for patients on NPH (0.05 +/- 0.03 per patient every 30 days) and for UL (0.07 +/- 0.04 per patient every 30 days) insulin. There was no significant difference for glycemic control between the NPH and UL groups overall (HbAlc at the end of the study: 7.6 +/- 0.1 vs. 7.7 +/- 0.1%, respectively), and by study's end a similar number of patients in the NPH and the UL groups needed to be switched to twice daily basal insulin (21 and 24%, respectively). Patients requiring twice-daily injections of basal insulin had a longer duration of diabetes (17.8 +/- 1.5 vs. 14.0 +/- 0.8 years, P < 0.05) and a highest baseline HbAlc (8.6 +/- 0.1 vs. 8.0 +/- 0.1%, P < 0.002) and were significantly older (38 +/- 2 vs. 34 +/- 1 years, P < 0.007). Patients who were switched to twice-daily NPH insulin had lower HbAlc levels at study's end compared with those switched to twice-daily UL insulin (7.7 +/- 0.2 vs. 8.2 +/- 0.3%), but this difference was not statistically significant. Distribution of hypoglycemia across the day was also similar in both groups. CONCLUSIONS: UL or NPH insulin, when used as the basal insulin for multiple injection regimens, results in similar glycemic control in patients using insulin lispro before meals. However, in patients who require a second injection of basal insulin, NPH insulin appears to provide lower prebreakfast and prelunch glucose levels compared with UL insulin.
Effects of aerobic or resistance exercise and/or diet on glucose tolerance and plasma insulin levels in obese men.
Authors: Rice B , Janssen I , Hudson R , Ross R
Published: March 2007

OBJECTIVE: This study had two objectives. First, we examined whether the influence of diet combined with either aerobic (DA) (n = 10) or resistance (DR) (n = 10) exercise has effects on insulin and glucose levels that are different in obese men. Second, we tried to determine whether the combination of diet and exercise is associated with improvements in insulin and glucose levels that are greater than those associated with diet alone (DO) (n = 9). RESEARCH DESIGN AND METHODS: Insulin and glucose levels were measured after an overnight fast and a 75-g oral glucose challenge (OGTT). Visceral adipose tissue (AT), subcutaneous AT, and skeletal muscle were measured by magnetic resonance imaging (MRI) before and after treatment (16 weeks). RESULTS: Reductions in weight (12.4 +/- 3.8 kg) and in visceral (37 +/- 15.1%) and subcutaneous AT (24.3 +/- 8.6%) were not different between treatments (P > 0.05). Skeletal muscle was maintained in the DA and DR groups but was reduced (7.3 +/- 2.8%) in the DO group (P < 0.05). Independent of treatment, fasting glucose and OGTT glucose did not change (P > 0.05). However, fasting insulin, OGTT insulin, and the insulin-to-glucose ratio decreased within all treatments (P < 0.05). Reductions in the OGTT insulin area under the curve were greater (P < 0.05) within the DA (52 +/- 12%) and DR (42 +/- 17%) treatments than in the DO (20 +/- 15%) treatment. Collapsed across group, reductions in visceral AT were related to reductions in fasting and OGTT glucose (P < 0.05), whereas reductions in abdominal subcutaneous AT correlated with reductions in fasting insulin (P < 0.05). CONCLUSIONS: Weight loss induced by diet and aerobic or resistance exercise has similar positive effects on lowering fasting and OGTT insulin values that are greater than those with diet alone. Because changes in glucose and insulin were related to reductions in visceral and abdominal subcutaneous AT, we conclude that reduction in abdominal obesity consequent to diet and exercise-induced weight loss is important for attaining improvements in plasma insulin levels, observations that strengthen the concept that abdominal obesity has an important role in mediating insulin resistance.
Black-white differences in risk of developing retinopathy among individuals with type 2 diabetes.
Authors: Harris E L , Sherman S H , Georgopoulos A
Published: March 2007

OBJECTIVE: To assess racial differences in risk of developing retinopathy among individuals with type 2 diabetes, after taking into account differences in the distribution of risk factors for retinopathy. RESEARCH DESIGN AND METHODS: The participants were 105 individuals with type 2 diabetes, aged 40-69 years, who had no evidence of retinopathy at the time of a diabetic eye disease screening project. After an average of 4 years of follow-up, the subjects were reevaluated using nonmydriatic funds photography. RESULTS: Retinopathy occurred more often among black than white participants (50 vs. 19%). This difference could not be explained by differences in risk factors for retinopathy or potential confounders (odds ratio [95% CI] 2.96 [1.00-8.78] after adjustment for level of glycosylated hemoglobin, systolic blood pressure, type of diabetes treatment, and sex). CONCLUSIONS: These results are consistent with the concept that racial differences in risk of developing retinopathy exist among individuals with type 2 diabetes and that these differences may be caused by differential (genetic) susceptibility to the adverse effects of increased levels of blood glucose and/or blood pressure. Discovery of the etiology of this differential susceptibility would allows us to identify and target secondary prevention efforts to individuals with type 2 diabetes who are at increased risk of retinopathy.