bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Training in Obese Diabetic Patients
Authors: Björntorp Per A
Published: March 2007

The consensus of studies in non-insulin-dependent diabetes mellitus (NIDDM) seems to be that exercise has beneficial effects not only on glucose metabolism and insulin sensitivity, but also on elevated plasma lipids, blood pressure, and obesity frequently following NIDDM. Feasibility of effective physical training programs in subjects suffering from NIDDM seems, however, questionable on a large scale because NIDDM is found mainly in physically inactive subjects over the age of 50. In such individuals, cardiovascular complications may also prevent physical activity of sufficient intensity. Although direct information is limited, the possibility remains that regular exercise may prevent or postpone clinical NIDDM, particularly by preventing the development of obesity.
Diabetic Neuropathies
Authors: Vinik Aaron I , Holland Marie T , Beau Jean M Le , Liuzzi Francis J , Stansberry Kevin B , Colen Larry B
Published: March 2007

Diabetic neuropathy is a common complication of diabetes that may be associated both with considerable morbidity (painful polyneuropathy, neuropathic ulceration) and mortality (autonomic neuropathy). The epidemiology and natural history of diabetic neuropathy is clouded with uncertainty, largely caused by confusion in the definition and measurement of this disorder. We have reviewed various clinical manifestations associated with somatic and autonomic neuropathy, and we herein discuss current views related to the management of the various abnormalities. Although unproven, the best evidence suggests that near-normal control of blood glucose in the early years after diabetes onset may help delay the development of clinically significant nerve impairment. Intensive therapy to achieve normalization of blood glucose also may lead to reversibility of early diabetic neuropathy, but again, this is unproven. Our ability to manage successfully the many different manifestations of diabetic neuropathy depends ultimately on our success in uncovering the pathogenic processes underlying this disorder. The recent resurgence of interest in the vascular hypothesis, for example, has opened up new avenues of investigation for therapeutic intervention. Paralleling our increased understanding of the pathogenesis of diabetic neuropathy, refinements must be made in our ability to measure quantitatively the different types of defects that occur in this disorder. These tests must be validated and standardized to allow comparability between studies and more meaningful interpretation of study results.
Glycemic Control and Peripheral Nerve Conduction in Children and Young Adults After 5–6 Mo of IDDM
Authors: Allen Catherine , Duck Stephen C , Robert L Sufit , Swick Herbert M , D'alessio Donn J ,   for the Wisconsin Diabetes Registry
Published: March 2007

Objective

A cohort of people (n = 86) was examined in the first few months after insulin-dependent diabetes mellitus (IDDM) diagnosis to evaluate the effect of hyperglycemia on nerve conduction velocities and latencies.

Research Design and Methods

Unselected cases with IDDM, who were 6–29 yr of age, were identified at diagnosis from a large, geographically defined area of southern Wisconsin. Peripheral nerve conduction was measured on a sample from this cohort.

Results

Peroneal nerve conduction velocity was significantly inversely related to glycosylated hemoglobin (P <0.05, age and height adjusted). All other nerve conduction velocities and latencies (median motor, median sensory, and sural) showed the same tendency, but the associations were not statistically significant. Twenty-four-hour urine C-peptide and duration of diabetes (3–11 mo) were not consistently related to nerve conduction parameters after controlling for age and height.

Conclusions

These findings suggest that as early as 5–6 mo after diabetes diagnosis, and at a time frequently characterized by partial remission of IDDM, hyperglycemia has a role in the acute slowing of nerve conduction velocity. Other factors such as residual endogenous insulin production do not appear to influence these early changes.
Impact of Associated Conditions on Glycemic Control of NIDDM Patients
Authors: Ferrannini Eleuterio , Stern Michael P , Galvan Alfredo Quinones , Mitchell Braxton D , Haffner Steven M
Published: March 2007

Objective

To assess the impact of associated conditions (obesity, dyslipidemia, and hypertension) on the glycemic control of non-insulin-dependent diabetes mellitus (NIDDM) patients under home-life conditions.

Research Design and Methods

We analyzed the metabolic data of 271 NIDDM patients (89% Mexican American) screened in a population-based survey (the San Antonio Heart Study).

Results

Obesity was present in 77% of the patients, hypertension in 23%, hypertriglyceridemia (serum triglycerides >2.9 mM) in 23%, and hypercholesterolemia (serum total cholesterol <6.5 mM) in 14%. Forty percent of the patients had two or more comorbid conditions. With the use of a multiple linear regression model, which was adjusted for age, sex, ethnicity, distribution of body fat (waist-hip ratio), plasma insulin, and treatment (of both diabetes and hypertension), we found that the presence of higher serum triglyceride concentrations was associated with significantly higher plasma glucose levels both in the fasting state (1.4 mM, P <0.001) and 2 h after an oral glucose load (1.2 mM, P = 0.003). The presence of obesity, hypertension, or high serum cholesterol levels was not associated with significant changes in glycemic control. When the entire group was stratified by diabetes treatment (untreated n = 89, diet n = 75, oral agents n = 82, insulin n = 25) and after adjusting for age, sex, ethnicity, and waist-hip ratio, only fasting and 2-h plasma glucose and insulin concentrations were significantly different across treatment groups, with diet and oral agents being associated with higher fasting (P <0.001) and postglucose (P <0.005) plasma glucose levels and lower plasma insulin concentrations (P <0.005) compared with newly diagnosed patients. Neither serum lipids nor blood pressure differed across treatment.

Conclusions

In NIDDM patients under home-life conditions, higher serum triglycerides are associated with higher fasting and postglucose hyperglycemia regardless of antidiabetic treatment. The presence of obesity, hypertension, or high serum cholesterol levels is not associated with significant changes in glycemic control.
Dichloroacetate
Authors: Stacpoole Peter W , Greene Yvonne J
Published: March 2007

Dichloroacetate (DCA) represents a potentially novel class of oral antidiabetic agents that reduce blood glucose and lipids without stimulating insulin secretion. DCA reduces blood glucose by inhibiting hepatic glucose synthesis and stimulating glucose clearance and use by peripheral tissues. A major site of action of the drug is pyruvate dehydrogenase (PDH), the rate-limiting enzyme of aerobic glucose oxidation. Stimulation of PDH by DCA increases peripheral oxidation of alanine and lactate, thereby interrupting the Cori and alanine cycles and reducing the availability of three-carbon precursors for gluconeogenesis. In experimental models of ketosis, DCA reduces ketonemia and ketonuria while significantly lowering blood glucose.

DCA inhibits hepatic triglyceride and cholesterol biosynthesis. Short-term studies in patients with non-insulin-dependent diabetes have demonstrated a capacity of the drug to markedly reduce circulating a very-low-density lipoprotein cholesterol and triglyceride concentrations. In genetic models of insulin-dependent diabetes, oral administration of DCA significantly reduces insulin requirements and blood levels of glucose and triglycerides.

Several derivatives of DCA have been synthesized and found to have biological activity in animals. Further work is required to determine whether DCA and its analogues may be safe and effective agents for chronic treatment of the carbohydrate and lipid abnormalities of human diabetes.
Homogeneity in Pattern of Decline of β-Cell Function in IDDM: Prospective study of 204 consecutive cases followed for 7.4 yr
Authors: Snorgaard Ole , Lassen Lassen H , Binder Christian
Published: March 2007

OBJECTIVE

To study the natural history of β-cell function from onset of IDDM to expected deterioration of insulin (C-peptide) secretion and to identify different patterns of decline, if any.

RESEARCH DESIGN AND METHODS

A cohort of 204 consecutive newly diagnosed IDDM (clinical criteria) patients were followed prospectively for 7.4 yr (range 6–9 yr), measuring fasting C-peptide at onset, 1, 3, 6, 9, 12, and then every 6 mo until 106 wk (range 104–135 wk). Then, postprandial C-peptide was measured.

RESULTS

Fasting C-peptide was 0.17 nM (range 0.11–0.25 nM) at onset followed by an annual increase rate of 0.16 nM/yr (range 0.06–0.48 nM/yr) to a peak of 0.28 nM (range 0.23–0.34 nM/yr) after 25 wk (range 12–39 wk). The subsequent annual decline rate of fasting C-peptide was 0.08 (0.05–0.12) and of postprandial C-peptide 0.03 nM/yr (range 0.02–0.06 nM/yr). None of these parameters showed bimodality in their distribution. However, some parameters were important. In men, fasting C-peptide at onset was lower, but the initial C-peptide increase rate was more pronounced compared to women. Furthermore, insulin-free remission was related to higher C-peptide levels throughout the study. C-peptide was higher during the 1st yr of diabetes in subjects > 30 yr of age at onset compared with younger diabetic patients. Stepwise multiple regression analysis showed that age, male sex, and fasting C-peptide at onset were of some predictive value for the C-peptide levels at 5 yr. However, simple group comparisons revealed no significant differences.

CONCLUSIONS

No major heterogeneity exists in the pattern of decline of β-cell function in IDDM, although small differences in pattern could be identified in both sexes, in different age-groups, and in relation to achieving insulin-free remission.
Granulocytes and Three-Phase Bone Scintigraphy for Differentiation of Diabetic Gangrene with and Without Osteomyelitis
Authors: Ritter Michael M , Richter Werner O , Leinsinger Gerda , Kirsch Carl Martin , Schwandt Peter
Published: March 2007

OBJECTIVE

In diabetic gangrene, concomitant osteopathy and soft-tissue infection often render laboratory and roentgenographic signs unreliable as indicators of osteomyelitis. In this situation, scintigraphic methods can be helpful.

RESEARCH DESIGN AND METHODS

Relying on the long-term clinical course as the final indicator of presence or absence of osteomyelitis, we prospectively compared in 31 patients three-phase bone scintigraphy with either indium-labeled autologous granulocytes (n = 20) or 123 I-labeled antibodies against granulocytes (n = 11).

RESULTS

Three-phase bone scintigraphy and imaging with indium-labeled autologous granulocytes yielded sensitivities and specificities of 95 and 70% for bone scintigraphy and 77 and 100% for granulocyte scintigraphy, respectively. One patient with severe angiopathy and proved osteomyelitis had a negative bone scintigraphy but a positive scintigraphy with labeled antibodies against granulocytes. One patient with aseptic bone necrosis presented with a formally false positive result with both methods.

CONCLUSIONS

In contrast to former retrospective studies, three-phase bone scintigraphy compares very well with granulocyte scintigraphy. The care of most patients can be managed with clinical data and this widely available scintigraphic method.
Blood Pressure Elevation Versus Abnormal Albuminuria in the Genesis and Prediction of Renal Disease in Diabetes
Authors: Mogensen Carl Erik , Hansen Klavs Würgler , Østerby Ruth , Damsgaard Else Marie
Published: March 2007

A number of risk factors associated with the development of diabetic nephropathy has been described, such as elevated blood pressure, poor metabolic control, hyperlipidemia, and smoking. Abnormal albuminuria also is associated with progression of renal disease, but has until recently been considered principally a marker of disease activity rather than a risk factor. This article discusses the role of elevated blood pressure versus abnormal albuminuria in a genesis and prediction of renal disease in diabetes. Controversy exists regarding parental disposition to hypertension and early blood pressure elevation in the course of diabetes, but all studies agree that elevated blood pressure—in the presence of abnormal albuminuria—constitutes a risk factor. Because abnormal albuminuria is associated with progression disease, it may itself be a risk factor because increased macromolecular traffic over the glomerular membrane may produce glomerulopathy. Problems related to blood pressure measurement are important, and 24-h recordings of blood pressure may be recommended in some situations. Regarding renal structure, preliminary results suggest that structural lesions precede blood pressure elevation. The solid end point for evaluation of renal disease progression is the fall rate of GFR, with abnormal albuminuria as an intermediate end point, also in drug trials. Abnormal albuminuria may constitute a new indication for antihypertensive treatment, being, as it is, a clear indicator of organ damage, whereas elevated blood pressure with normal AER may not increase risk substantially.
The Effect of Glyburide on β-Cell Sensitivity to Glucose-Dependent Insulinotropic Polypeptide
Authors: Meneilly Graydon S , Bryer-Ash Michael , Elahi Dariush
Published: March 2007

Objective— To assess whether treatment with glyburide alters β-cell sensitivity to GIP in NIDDM patients.

Research Design and Methods— We studied 5 untreated NIDDM patients in a meal study (Ensure, 240 ml/M2) and a 2-h hyperglycemic glucose clamp study (glucose 5.4 mM above fasting). From 60 to 120 min of the clamp, GIP was infused in a primed continuous manner at a rate of 2 pmol·kg−1·min−1. Subjects then were treated with glyburide. After they had been on a stable dose of medication for 1 mo, the meal study and glucose clamp studies were repeated.

Results— In response to treatment, a decrease in fasting glucose and an increase in weight was observed (12.8 ± 1.8 vs. 8.5 ± 0.8 mM and 74.3 ± 6.3 vs. 76.1 ± 6.3 kg, respectively, P < 0.05). In response to the meal study, the AUC for glucose was less, for insulin was increased, and for GIP was unchanged after treatment (16.9 ± 2.1 vs. 12.6 ± 6.9 mM, P <0.05; 161 ± 47 vs. 242 ± 60 pM, P < 0.05; and 199 ± 22 vs. 219 ± 18 pM, respectively). During the hyperglycemic clamp, steady-state glucose and 90- to 120-min GIP values were equivalent before and after treatment (18.0 ± 1.3 vs. 18.3 ± 1.3 mM and 302 ± 59 vs. 298 ± 37 pM, respectively). The 90b–120 min insulin responses to the hyperglycemic clamp were greater after therapy (123 ± 37 vs. 283 ± 80 pM, P < 0.05) reflecting increased β-cell responses to GIP.

Conclusions— We conclude that glyburide enhances β-cell sensitivity to GIP.
Decrease of Glomerular Hyperfiltration in Short-Term Diabetic Adolescents Without Microalbuminuria
Authors: Bognetti Emilio , Meschi Franco , Bonfanti Riccardo , Gianolli Luigi , Chiumello Giuseppe
Published: March 2007

Objective— This study has been designed to follow prospectively the GFR and UAE of young patients with short-term IDDM and normal UAE.

Research Design and Methods— The study population consisted of 19 patients with glomerular hyperfiltration and 19 patients with normal GFR, matched for duration of diabetes and age. GFR has been assessed by radioisotopic tracer and UAE by RIA at the beginning of the study and after 30.5 ± 10.4 mo of follow-up.

Results— GFR decreased in the two groups but Δ GFR of patients with glomerular hyperfiltration was greater than Δ GFR of patients with normal GFR (0.83 ± 0.55 vs. 0.28 ± 0.63 ml·min−1·mo−1; P < 0.01). UAE, BP, and prevalence of microalbuminuria were comparable between the two groups at follow-up. Rate of fall of GFR was positively correlated with initial GFR (r = 0.59, P < 0.001) but not with initial UAE, BP, or changes in HbA1C, UAE, BP, or pubertal development during follow-up.

Conclusions— Investigation of kidney function in children and adolescents with IDDM over a 3-yr follow-up period shows that glomerular hyperfiltration is characterized by a greater decline in GFR without an increased rate of appearance of microalbuminuria, than in patients with normal GFR.
Determinants of Clinical Remission in Recent-Onset IDDM
Authors: Hramiak Irene M , Dupre John , Finegood Diane T
Published: March 2007

Objective— To assess the relationship of SI and insulin secretion (C-peptide levels) to remission status in recent-onset IDDM.

Research Design and Methods— We followed 22 newly diagnosed patients, of whom 16 received immunomodulatory treatment with low-dose (5 mg·kg−1·day−1) CsA and/or short-term (72 h) methylprednisolone and 6 received standard insulin treatment, at 3-mo intervals for 12 mo. Insulin secretion was assessed by C-peptide levels and AIRglu, which was determined as the area under the insulin response curve, above the fasting level, from 0–10 min after a 0.3 g·kg−1·i.v. glucose xbolus. SI was assessed by the minimal model technique applied to a frequently sampled IVGTT. Clinical remission was defined in those patients who maintained normal range GHb and capillary blood glucose levels <7.8 mM premeal without insulin therapy for a minimum of 14 days.

Results— The rate of clinical remission was not different with immunomodulatory treatment; nor were the metabolic parameters of plasma C-peptide levels, AIRglu, and S1 different in the treatment groups. The mean plasma C-peptide level improved significantly at 3 mo and was maintained to 12 mo. AIRglu was grossly subnormal throughout, but a significant improvement was seen at 3 and 6 mo. Mean SI was normalized at 3 and 6 mo but not maintained beyond 9 mo. The maximum rate of clinical remission was seen at 6 mo.

Conclusions— Clinical remission in recent-onset IDDM patients is associated with improvement in both insulin secretion and SI. Although the improvement in basal C-peptide persisted, AIRglu increased only transiently and declined as loss of remission occurred in most patients. Loss of remission to an insulin-requiring state is associated with a decrease in SI.
Lower-Extremity Amputations in Diabetic and Nondiabetic Patients: A population-based study in eastern Finland
Authors: Siitonen Onni I , Niskanen Leo K , Laakso Markku , Siitonen Jukka T , Pyörälä Kalevi
Published: March 2007

Objective— To study the incidence of LEAs attributable to PVD in diabetic and nondiabetic patients. The age at first amputation, the level of amputation, the number of reamputations, and survival after amputation also were examined in the study populations.

Research Design and Methods— This retrospective study was based on a population of 253,000 inhabitants in eastern Finland. All patients with their first LEA performed during the period from 1 January 1978 to 31 December 1984 were identified from the registers of operation theaters in the study area. Furthermore, patient records and death certificates were reviewed. Amputations attributable to causes other than evident atherosclerotic vascular disease were excluded.

Results— Altogether, 477 patients (85 diabetic men, 127 nondiabetic men, 169 diabetic women, and 96 nondiabetic women) were identified. The overall LEA rate was 26.9/100,000 per yr, and the incidence increased strongly with age in both diabetic and nondiabetic patients. The age-adjusted amputation incidence per yr was 349.1/100,000 for diabetic men, 33.9/100,000 for nondiabetic men, 239.4/100,000 for diabetic women, and 17.2/100,000 for nondiabetic women. The proportion of peripheral (toe, leg) amputations was markedly higher in diabetic patients who also tended to have more reamputations during the follow-up than did nondiabetic subjects. The diabetic status per se was a statistically significant risk factor for mortality in women, but not in men.

Conclusions— Diabetic men and women had a 10.3- and 13.8-fold higher risk, respectively, for LEA.
Diabetes and Plasma Lipoproteins in Native Americans: Studies of the Pima Indians
Authors: Howard Barbara V
Published: March 2007

OBJECTIVE– To determine the effects of diabetes on plasma lipoproteins in Pima Indians, to identify metabolic determinants of these differences, and to examine the effects of various modes of diabetes therapy.

RESEARCH DESIGN AND METHODS— A series of studies was performed including a population survey of lipoprotein concentrations, kinetic studies of VLDL and LDL metabolism, and studies of the effects of weight loss, sulfonylureas, and high carbohydrate diets.

RESULTS— Population data established that diabetes was consistently associated with elevations in total and VLDL TGs and decreases in HDL cholesterol. Metabolic studies indicated multiple alterations in VLDL metabolism induced by NIDDM, including overproduction of VLDL TG, impaired clearance of VLDL TG and apoB, and decreases in adipose tissue lipoprotein lipase. Although changes in LDL concentrations accompanying NIDDM were minimal, the clearance of LDL appeared to be impaired and a higher proportion of VLDL was metabolized without conversion to LDL. There were significant changes in the flux of particles to the LDL compartment. Total and VLDL TG concentrations were found to be inversely related to rates of insulin-mediated glucose disposal, and HDL cholesterol concentrations were positively related to glucose disposal. These relationships between lipoproteins and insulin action were independent of adiposity and insulin, suggesting that insulin resistance may be involved with diabetes-induced changes in VLDL and HDL. Weight loss was associated with decreases in total and VLDL TG, decreases in total and LDL cholesterol, and improvements in the ratio of HDL to LDL cholesterol. Sulfonylurea therapy was associated with lower total and VLDL TGs and lower LDL cholesterol, but little change in HDL. Substitution of complex carbohydrates for saturated fat in the diet showed consistent and significant decreases in total and LDL cholesterol, no decreases in HDL cholesterol, or elevation of total or VLDL TG.

CONCLUSIONS— Studies suggest that there are multiple changes in plasma lipoproteins accompanying NIDDM in Pima Indians, but that many of these may be reversed by current modes of hypoglycemic therapy.
Insulin Therapy and Weight Change in Native-American NIDDM patients
Authors: Hickey Martin E , Hall Terri R
Published: March 2007

OBJECTIVE— To determine whether NIDDM patients exposed to insulin therapy in a clinical setting gain weight.

RESEARCH DESIGN AND METHODS— This study, an historical cohort chart review, was conducted at the IHS clinic on the Navajo Reservation in Northern Arizona. We studied 27 Native Americans with NIDDM and 102 Native-American nondiabetic control subjects.

RESULTS— Insulin therapy consisting of a mean of 105 U/day was associated with a mean weight gain of 3.0 ± 2.2 kg/yr. When insulin was discontinued or decreased, a mean weight loss of 5.2 ± 2.7 kg/yr was observed in the same patients. No significant weight gain was noted in 102 nondiabetic control subjects, nor in 20 of 27 insulin-treated patients given oral hypoglycemic agents before initial insulin therapy.

CONCLUSIONS— Insulin therapy appeared to be associated with weight gain in this group of NIDDM patients. This suggests that observations for weight gain be undertaken when treating NIDDM patients with insulin, because it may exacerbate the underlying pathophysiology of the disease.
Improvement of Diabetic Control and Acceptability of a Three-Injection Insulin Regimen in Diabetic Adolescents: A multicenter controlled study
Authors: Bougnères P F , Landais P , Mairesse A M , Jais J P , Jos J , Peyraud J , Wieliczko M C , Chavoix P , Garandeau P , Asensi D , Ythier H , Rouland V , Mazoyer T , Leturcq F , Raynaud E
Published: March 2007

Objective— To compare the effectiveness and acceptability of a three-injection insulin regimen with the conventional two-injection therapy in an unselected population of diabetic adolescents.

Research Design and Methods— Some 205 patients aged 10–18 yr with IDDM, who were previously treated with two daily insulin injections, were included without any selection into a randomized trial. They were either switched to three (regular prebreakfast, regular prelunch, and [regular + ultralente] predinner) or remained on two ([regular + intermediary] prebreakfast and predinner) subcutaneous injections. They were evaluated after 1 yr of treatment. The major criteria of outcome of efficacy were the concentration of GHb, the frequency of severe hypoglycemia and DKA, and body weight.

Results— Of the patients, 82% accepted the three-injection regimen, and 83% accepted the two-injection regimen. At entry into the trial, no significant differences appeared between the two treatment groups nor among patients refusing the allocated regimen. Significant explanatory variables predicting initial diabetes control were duration of disease and adherence to diet. GHb, decreased from 9.8 ± 0.1 to 9.3 ± 0.2% (P < 0.05) in the three-injection group, whereas it increased from 9.5 ± 0.3 to 9.8 ± 0.3% (P < 0.05) in the two-injection group, resulting in a modest (0.75%) but significant difference (P < 0.05) between GHb change in the two groups. The difference reached 1.4% (P < 0.0002) in patients with GHb > 11.2% at entry. The frequency of hypoglycemia and DKA was similar in the two groups. None of the parameters known to potentially influence glycemic control changed during the trial, and, therefore, the improvement of GHb could be attributed to the pattern of daily insulin distribution per se.

Conclusions— In the general diabetic adolescent population, the efficacy of a three-injection regimen is somewhat superior to that of a conventional two-injection regimen, particularly in patients previously poorly controlled. The acceptability of this regimen being excellent, its increased use should be considered in this age-group.
Neurophysiological Impairments in IDDM Patients During Euglycemia and Hypoglycemia
Authors: Lingenfelser Thomas , Buettner Ulrich W , Sommerwerck Urte , Renn Walter , Eggstein Manfred , Jakober Bernhard
Published: March 2007

OBJECTIVE

To test the hypothesis that latencies of evoked potentials in IDDM patients are delayed compared with healthy control subjects during euglycemia, and that insulin-induced hypoglycemia causes further latency delays of evoked potentials to occur.

RESEARCH DESIGN AND METHODS

We recruited 23 IDDM patients (27.9 ± 1.6 yr of age, HbA1c 6.7 ± 0.3%, without sensory or autonomic neuropathy) and 26 unequivocally healthy subjects who were carefully matched for sex, age, and body mass index to serve as the control group (18 men and 8 women, 28.4 ± 1.6 yr of age, 22.6 ± 0.7 kg/m2), for a controlled, prospective study. Sequential euglycemichypoglycemic clamps were performed with stable glycemic plateaus of 5.6, 3.3, 2.2, and 1.7 mM, at which the patients' and healthy control subjects' neurophysiological functions were evaluated. The methodological armamentarium included the measurement of brainstem auditory, middle-latency auditory, and somatosensory evoked potentials that assessed conduction velocity in corresponding neural structures and information processing in the midbrain and auditory cortex.

RESULTS

Multiple analysis of variance revealed a significant overall difference of brainstem auditory evoked potential latencies during euglycemia between the study group and healthy control group (F = 3.41, P < 0.03), which was mainly attributable to latency delays of wave III (F = 6.60, P < 0.02), V (F = 9.19, P < 0.01), and interpeak latency 1-V (F = 2.82, P < 0.07). Repeated analysis of variance measures detected a significant latency delay of the major wave Pa of the middle-latency auditory evoked potentials during hypoglycemia (F = 4.4, P < 0.02), which rapidly returned to normal after reinstitution of euglycemia.

CONCLUSIONS

In IDDM patients, chronic, structural CNS changes already appear at the brainstem level during euglycemia. Functional, reversible CNS changes, however, seem to emerge during acute deviation from glucose homeostasis in more rostral brain regions.
Effects of the Anatomical Region Used for Insulin Injections on Glycemia in Type I Diabetes Subjects
Authors: Bantle John P , Neal Lonzetta , Frankamp Lisa M
Published: March 2007

OBJECTIVE

Subcutaneous insulin is absorbed at different rates from different anatomical regions, but it is not clear how much the varying rates of absorption affect plasma glucose concentrations in diabetic subjects. To address this issue, subcutaneous injections of insulin in the abdomen were compared with subcutaneous injections of insulin in the thigh.

RESEARCH DESIGN AND METHODS

In a crossover trial, 22 type I diabetic subjects received, in random order, a test dose of regular insulin injected subcutaneously in the abdomen on one morning and in a thigh on another morning. The subjects also received, in random order, usual morning doses of NPH and regular insulins injected subcutaneously in the abdomen on one morning and in a thigh on another morning. The study was performed in the University of Minnesota General Clinical Research Center. Main outcome measures were plasma glucose and serum free insulin.

RESULTS

After injections of regular insulin in the abdomen, the peak postprandial increment in plasma glucose was 3.1 mM or 29% lower (P < 0.001), the peak increment in serum free insulin was 54 pM or 38% higher (P = 0.017), and the length of time required to achieve peak serum free insulin was significantly shorter than after injections of regular insulin in the thigh. After injections of NPH and regular insulins in the abdomen, the morning peak increment in plasma glucose was 2.5 mM or 18% lower (P = 0.008) than after injections of NPH and regular insulins in a thigh. However, no significant difference was observed in the afternoon peak increment in plasma glucose.

CONCLUSIONS

A subcutaneous injection of regular insulin in the abdomen produced a substantially greater reduction in plasma glucose than an injection of regular insulin in the thigh. Changing the injection site of regular insulin from the abdomen to the thigh had an effect equivalent to reducing the dose administered. With injections of NPH and regular insulin in combination, the influence of the region used for injection was less but still potentially important.
Lipoprotein Abnormalities in Well-Treated Type II Diabetic Patients
Authors: Manzato Enzo , Zambon Alberto , Lapolla Annunziata , Zambon Sabina , Braghetto Lorenzo , Crepaldi Gaetano , Fedele Domenico
Published: March 2007

OBJECTIVE

To investigate lipoprotein levels and composition in well-treated type II diabetic patients.

RESEARCH DESIGN AND METHODS

Cholesterol and triglyceride levels were measured in plasma, VLDL, LDL, and HDL in 120 type II diabetic patients in good to fair metabolic control (HbA1c, 7.2 ± 1.6%) and in 30 normal control subjects. ApoAI, AII, B, CII, CIII, and E levels in plasma were also determined.

RESULTS

The diabetic patients have significantly higher levels of mean plasma cholesterol (5.85 vs. 5.43 mM, P = 0.03), LDL triglycerides (0.41 vs. 0.31 mM, P = 0.003), and HDL triglycerides (0.24 vs. 0.19 mM, P = 0.02), whereas total triglycerides, VLDL cholesterol and triglycerides, LDL cholesterol, and HDL cholesterol are not significantly different from normal control subjects. ApoB (150 vs. 135 mg/dl, P = 0.02) and apoCIII (10.6 vs. 8.4 mg/dl, P = 0.01) are significantly higher in diabetic patients compared with control subjects. No significant differences are observed in all the parameters among diabetic patients treated with diet only, sulphonylurea, sulphonylurea plus biguanides, or insulin. Body weight is significantly related to VLDL lipids. The VLDL triglycerides are inversely related to the HDL cholesterol in both diabetic patients and control subjects. The VLDL triglycerides are directly related to the HDL triglycerides only in diabetic patients. No other lipid or lipoprotein parameters are significantly related to body weight or metabolic control.

CONCLUSIONS

Type II diabetic patients in good to fair metabolic control are characterized by minor alterations of the plasma lipids, but LDL and HDL triglycerides, apoB, and apoCIII are increased, thus indicating that the lipoprotein composition is altered, possibly because of an abnormal triglyceride metabolism and/or lipid transfer activity.
Oral Health in Patients With Type II Diabetes and Impaired Glucose Tolerance
Authors: Cherry-Peppers Gail , Ship Jonathan A
Published: March 2007

OBJECTIVE

To assess the influence of type II diabetes and impaired glucose tolerance on dental, periodontal, and oral mucosal tissues.

RESEARCH DESIGN AND METHODS

We examined 11 subjects with type II diabetes, 32 with impaired glucose tolerance, and 43 control subjects from the oral physiology component of the Baltimore Longitudinal Study of Aging. At the time of the study, none of the participants was taking medication nor being treated for any medical problems other than diabetes.

RESULTS

Only a few statistically significant dental and periodontal changes were apparent in the group with type II diabetes, and no oral mucosal differences existed between the diabetes and control groups. Dental, periodontal, and oral mucosal parameters in patients with impaired glucose tolerance were essentially indistinguishable from the other two groups.

CONCLUSIONS

These findings suggest that among well-controlled individuals with type II diabetes and impaired glucose tolerance, few appreciable differences are evident in oral health.
Lipoprotein(a) Concentration Shows Little Relationship to IDDM Complications in the Pittsburgh Epidemiology of Diabetes Complications Study Cohort
Authors: Maser Raelene E , Usher David , Becker Dorothy J , Drash Allan L , Kuller Lewis H , Orchard Trevor J
Published: March 2007

OBJECTIVE

To examine the potential associations of lipoprotein(a) and the complications of IDDM and their risk factors.

RESEARCH DESIGN AND METHODS

This report focuses on 186 individuals with IDDM (mean age = 34 yr) participating in a 10-yr prospective study examining various complications. Lp(a) concentrations were evaluated for those with and without complications.

RESULTS

A weak correlation was seen between Lp(a) and HbAj (r = 0.16, P < 0.05). Lp(a) concentrations were not significantly different for those with or without proliferative retinopathy, overt nephropathy, peripheral vascular disease, or definite myocardial infarction or angina. However, an inverse association (P < 0.05) was seen with distal symmetric polyneuropathy. These results were also confirmed by categorical analyses (i.e., Lp(a) levels <30 vs. >30 mg/dl).

CONCLUSIONS

These results suggest that any association of Lp(a) concentration with IDDM complications is likely to be weak or nonexistent. However, prospective studies are needed before its full role can be determined.
Attitudes and Behaviors of Primary Care Physicians Regarding Tight Control of Blood Glucose in IDDM Patients
Authors: Tuttleman Marilyn , Lipsett Lois , Harris Maureen I
Published: March 2007

OBJECTIVE

To evaluate attitudes and practices of primary-care physicians toward tight blood glucose control in IDDM.

RESEARCH DESIGN AND METHODS

A mail and telephone questionnaire survey was conducted on a systematic, stratified sample of 1429 family-practice physicians, general practitioners, internists, and pediatricians in active practice in the United States who treated patients with IDDM. Physicians were asked about methods they used for clinical and laboratory assessment of blood glucose control and about their attitudes and beliefs in treating IDDM. They were asked also what they consider to be acceptable ranges for blood glucose and HbA1 in IDDM patients. A score was developed reflecting three criteria for tight blood glucose control: fasting glucose 70–120 mg/dl (3.9–6.7 mM), 2-h postprandial glucose <180 mg/dl (<10 mM), and HbA1 <8% (the nondiabetic value was specified as 5–7%). Physicians were accorded one point when their acceptable range agreed with an intensive treatment criterion (range for score 0–3).

RESULTS

Only 31% of physicians agreed with all three criteria for tight control of blood glucose; 37% agreed with none or only one of the standards. Pediatricians were particularly low in their agreement with the HbA1 standard. Physicians who agreed with one of the three criteria often did not agree with the other two. With increasing value for the score, there was a greater proportion of physicians whose management practices (e.g., frequent measurement of HbA1 multiple insulin injections, patient SMBG, use of dietitian/educator in care of patients) are conducive toward tight control of blood glucose. However, even among physicians with a score of 3, HbA1 was ordered infrequently, three or more insulin injections/day was prescribed rarely, patient SMBG was less than fully endorsed, and both a dietitian and diabetes educator were used by a minority of physicians.

CONCLUSIONS

It appears that primary-care physicians are not fully aware of recommended criteria for intensive treatment of blood glucose in IDDM patients or of the importance of multiple insulin injections, use of HbA1; and patient SMBG. Physician practice behaviors are less than optimal for intensive management of IDDM patients, even among physicians who agree with all three standards for intensive treatment of blood glucose in IDDM.
Vascular Dysfunction Detected by a Simplified Venous Occlusion Test in NIDDM Patients
Authors: Mizuno Akira , Isobe Junichi , Shima Kenji
Published: March 2007

Objective— To elucidate the relationship between angiopathies and vascular function evaluated by a simplified venous occlusion test in patients with NIDDM.

Research Design and Methods— The serum concentration of FDP was measured before and 5 min after venous occlusion in 23 NIDDM patients, 11 patients with cerebrovascular accident, and 10 age-matched healthy control subjects.

Results— The increment of serum FDP level after venous occlusion was significantly less in patients with NIDDM (60.6 ± 33.5 to 81.5 ± 49.6 ng/ml) and in those with cerebrovascular accident (101.4 ± 51.5 to 116.2 ± 47.2 ng/ml) than in control subjects (79.9 ± 41.0 to 148.8 ± 65.4 ng/ml). The increment of serum FDP after venous occlusion in NIDDM patients with macroangiopathy was significantly lower than that in those without macroangiopathy.

CONCLUSION— The responsiveness of fibrinolytic activity to venous occlusion was significantly less in NIDDM patients with macroangiopathy, as in patients with cerebrovascular accident, compared with that in healthy control subjects.
Increased Levels of Cow's Milk and β-Lactoglobulin Antibodies in Young Children With Newly Diagnosed IDDM
Authors: Savilahti Erkki , Saukkonen Tero T , Virtala Esa T , Tuomilehto Jaakko , Åkerblom Hans K ,   The Childhood Diabetes in Finland Study Group
Published: March 2007

Objective— To investigate the humoral immune response to cow's milk in pediatric patients with newly diagnosed IDDM.

Research Design and Methods— We measured IgA, IgG, and IgM antibodies to the proteins of cow's milk and to β-lactoglobulin by an enzyme-linked immunosorbent assay. Samples from 706 pediatric patients with newly diagnosed IDDM were available. We used two comparison groups: 105 patients < 7 yr old had an unrelated age-matched control subject, and samples from 456 3- to 14-yr-old nondiabetic siblings also were available.

Results— Patients < 3 yr of age had a markedly higher median level of IgG and IgA antibodies to cow's milk compared with the control subjects (P = 0.03 and 0.002, respectively), IgG antibodies to β-lactoglobulin also were higher (P = 0.03). Older groups of diabetic patients, 3.0–6.9 and 7.0–14.9 yr of age, had significantly higher levels of IgA antibodies to cow's milk and β-lactoglobulin than the age-matched comparison groups of both unrelated control subjects and nondiabetic siblings, although the median values of the diabetic patients were closer to those of the comparison groups than in the youngest groups. Nondiabetic siblings had higher levels of IgA cow's milk antibodies than unrelated control subjects of similar ages (3–6.9 yr of age) (P = 0.03). The 14 siblings contracting IDDM during the follow-up showed no change in the levels of cow's milk or β-lactoglobulin antibodies in relation to the clinical diagnosis.

Conclusions— The results indicate an abnormally strong humoral response to the proteins of cow's milk, particularly in young IDDM patients and, to a lesser extent, in their siblings. We infer that the proteins of cow's milk may trigger the autoimmune process of IDDM.
HLA-DQβ Typing and Non-Asp57 Alleles in IDDM and Nondiabetic Subjects in New Zealand
Authors: Forbes Louisa V , Brown Laurie J , Scott Russell S
Published: March 2007

OBJECTIVE

To determine the frequency of IDDM risk-associated HLA-DQβ alleles in New Zealanders with IDDM and nondiabetic control subjects, and to examine these as susceptibility markers in relation to IDDM incidence.

RESEARCH DESIGN AND METHODS

HLA-DQβ typing was conducted in 55 juvenile-onset IDDM subjects diagnosed between 1990 and 1992, and 53 nondiabetic control subjects. Allele typing was conducted by a polymerase chain reaction-restriction fragment-length polymorphism technique. All subjects were residents of Canterbury, New Zealand. IDDM incidence data were obtained from the Canterbury, New Zealand, Diabetes Registry.

RESULTS

The frequency of the susceptibility genotype DQβ*0201/0302 was 43.6 and 5.7% in the IDDM and control groups, respectively, reflecting the increased prevalence of allele 0302 in the IDDM group. Alleles 0301, 0501, and 0602.3 were more prevalent in the control group than the IDDM group. The frequency of non-Asp57 alleles was 90.9 and 61.3% in the IDDM and control groups, respectively. Overall, the HLA-DQβ allele distribution was similar to reports from other Caucasian populations. The 0- to 19-yr age-specific IDDM incidence rate over the period in which the diabetic subjects were diagnosed was 19.5/100,000 person-yr, the highest levels observed in Canterbury over the last decade. Our relatively high background prevalence of non-Asp57 alleles and high IDDM incidence rates were similar to results from some Scandinavian and other hotspot populations.

CONCLUSIONS

HLA-DQβ alleles are genetic susceptibility markers in New Zealand, and other Caucasian populations. Peak IDDM incidence levels observed in 1990–1992 in our population are in accordance with a high background population prevalence of non-Asp57 alleles. These results suggest that the high Canterbury incidence rates may be due to a large HLA-DQβ non-Asp57 at-risk population.
Alterations in Glucose Metabolism in the Elderly Patient with Diabetes
Authors: Meneilly Graydon S , Dawson Keith , Tessier Daniel
Published: March 2007

Objective— To determine the alterations in glucose metabolism in elderly patients with NIDDM.

Research Design and Methods— We studied 9 healthy elderly control subjects (73 ± 1 yr of age; body mass index 25.7 ± 0.4 kg/m2) and 9 untreated elderly NIDDM patients (72 ± 2 yr of age; BMI 25.9 ± 0.5 kg/m2). Each subject underwent a 3-h oral glucose tolerance test (40 g/m2); a 2-h hyperglycemic glucose clamp study (glucose 5.4 mM above basal); and a 4-h euglycemic insulin clamp (40 mM · m2 · min−1). Tritiated glucose methodology was used to measure glucose production and disposal rates during the euglycemic clamp.

Results— Patients with NIDDM had a higher fasting glucose (9.3 ± 0.3 vs. 5.1 ± 0.1 mM in control subjects vs. NIDDM patients, respectively, P < 0.001) and a greater area under the curve for glucose during the OGTT (16.0 ± 0.6 vs. 6.7 ± 0.3 mM in control subjects vs. NIDDM patients, respectively, P < 0.01) than the healthy control subjects. During the hyperglycemic clamp, patients with NIDDM had an absent first-phase insulin response (112 ± 6 vs. 250 ± 31 pM in control subjects vs. NIDDM patients, respectively, P < 0.01), and a blunted second-phase insulin response (159 ± 11 vs. 337 ± 46 pM in control subjects vs. NIDDM patients, respectively, P < 0.01). Before the euglycemic clamp, fasting insulin (99 ± 5 vs. 111 ± 10 pM in control subjects vs. NIDDM patients, respectively) and hepatic glucose production (11.8 ± 0.7 vs. 11.5 ± 0.5 μmol · kg−1 μ min−1 in control subjects vs. NIDDM patients, respectively) were similar. Steady-state (180–240 min) glucose disposal rates during the euglycemic clamp were slightly, but not significantly, higher in the normal control subjects (36.5 ± 1.1 vs. 33.1 ± 1.9 μmol · kg−1 · min−1 in control subjects vs. NIDDM patients, respectively, NS).

Conclusions— We conclude that NIDDM in nonobese elderly subjects is characterized by a marked impairment in insulin release. This may be attributable to the toxic effects of chronic hyperglycemia on the β-cell. When compared with age-matched control subjects, the NIDDM patients showed no increase in fasting insulin or hepatic glucose production, and insulin resistance was mild.
Long-Term Randomized Placebo-Controlled Double-Blind Therapeutic Comparison of Glipizide and Glyburide: Glycemic control and insulin secretion during 15 months
Authors: Birkeland Kåre I , Furuseth Kristian , Melander Arne , Mowinckel Petter , Vaaler Stein
Published: March 2007

OBJECTIVE

To examine the long-term (15 months) effects on glycemic control and insulin secretion of glipizide and glyburide treatment in patients with noninsulin- dependent diabetes mellitus (N1DDM).

RESEARCH DESIGN AND METHODS

Prospective, randomized, doubleblind, placebo-controlled study on 46 NIDDM patients comparing fasting levels and test-meal responses of glucose and insulin during 15 months of follow-up.

RESULTS

A comparable reduction in HbA1c levels by both agents versus placebo was observed throughout the study period, but after a marked initial reduction in both sulfonylurea groups, all three groups showed gradually increasing HbA1c levels. However, both glipizide and glyburide achieved and maintained lowered postprandial glucose levels and increased fasting and postprandial insulin levels compared with placebo.

CONCLUSIONS

Both glipizide and glyburide may achieve and maintain glycemic reduction and stimulation of insulin secretion during long-term treatment. However, these agents do not prevent the gradual increase in overall glycemia that develops over time in NIDDM patients.
Establishment of Time-Action Profiles for Regular and NPH Insulin Using Pharmacodynamic Modeling
Authors: Woodworth James R , Howey Daniel C , Bowsher Ronald R
Published: March 2007

OBJECTIVE

To provide distinct definitions and quantify the establishment of onset, peak, and duration of action for insulins.

RESEARCH DESIGN AND METHODS

We administered single subcutaneous doses of 10 U regular insulin to 10 volunteer subjects and 25 U NPH insulin to 6 healthy male volunteer subjects on separate occasions. Each dose was given after an overnight fast during a glucose clamp to maintain an euglycemic state. We measured serum insulin concentrations and glucose infusion rates (GIR) from frequent blood sampling after each treatment. Serum insulin concentrations were related to GIR values at each collection time and a counter-clockwise hysteresis resulted. An effect compartment model was used to simultaneously describe the pharmacokinetics and pharmacodynamics of each insulin and to resolve the hysteresis.

RESULTS

From the resulting relationship, GIR could then be predicted, with onset and duration of action reflecting the time when effect compartment concentrations initially exceeded then declined below a 10% maximum possible effect (Emax) level. Ninety-five percent confidence intervals were constructed allowing a predictive range of values. For regular insulin, a mean onset of 0.75 h, peak of 2 h, and duration of 6 h was estimated. Mean values were also produced with NPH, with an onset of 3 h, peak of 6–7 h, and a duration of 13 h estimated.

CONCLUSIONS

This method estimates the onset, peak, and duration of insulin action. Although these estimates were from single doses, we believe they can provide good estimations of insulin activity.