bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulation of Insulin Secretion by Fructose Ingested With Protein in People With Untreated Type 2 Diabetes
Authors: Gannon Mary C , Nuttall Frank Q , Grant Charles T , Ercan-Fang Sean , Ercan-Fang Nacide
Published: March 2007

OBJECTIVE

Ingested protein provides substrate for gluconeogenesis and strongly stimulates insulin and glucagon secretion, but it has little effect on the glucose concentration in people with type 2 diabetes. Ingested fructose also is a substrate for gluconeogenesis, modestly stimulates insulin and glucagon secretion, and has little effect on the plasma glucose. Therefore we were interested in determining if ingestion of fructose along with protein would result in an additive, greater than additive, or less than additive effect on circulating insulin, glucagon, and glucose concentrations.

RESEARCH DESIGN AND METHODS

Seven male subjects with untreated type 2 diabetes were fasted overnight and then were given either 25 g fructose, 25 g protein, 25 g fructose plus 25 g protein, or water only at 0800. Subjects also ingested 50 g glucose on two separate occasions. Plasma glucose, insulin, C-peptide, glucagon, α-amino nitrogen, urea nitrogen, nonesterified fatty acids, and triglyceride concentrations were determined over the subsequent 5 h.

RESULTS

The glucose concentration was only modestly increased and the area responses were similar when protein, fructose, or the combination was ingested. Thus, the glucose response to the combination was less than additive. The insulin area response to protein was 2.5-fold greater than to fructose, and the response to the two nutrients was additive and quantitatively similar to the response to 50 g glucose. The glucagon area response was less than additive, i.e., there was an interaction between the protein and fructose that resulted in a smaller than expected response.

CONCLUSIONS

When protein and fructose were ingested together, the insulin response was similar to that following ingestion of 50 g glucose. It also was as expected based on the response to the individual nutrients. In contrast, the glucose and glucagon responses were significantly less than expected. These data may be useful in dietary planning for subjects with type 2 diabetes.
The Epidemiology and Cost of Inpatient Care for Peripheral Vascular Disease, Infection, Neuropathy, and Ulceration in Diabetes
Authors: Currie Craig J , Morgan Christopher LL , Peters John R
Published: March 2007

OBJECTIVE

To describe the epidemiology and costs of the acute care of peripheral vascular disease, infection, neuropathy, and ulceration in a U.K. population with special consideration of those patients with diabetes.

RESEARCH DESIGN AND METHODS

Routine data describing inpatient care for a 4-year period were analyzed (financial years 1991/1992 to 1994/1995). These data had undergone record-linkage to draw together records from the same patients, and records of patients with diabetes were flagged. Cost estimates were determined by attributing a diagnosis-related group cost-weight to each record.

RESULTS

A total of 4,245 admissions (1.2% of all admissions) had a primary diagnosis of peripheral vascular disease, infection, neuropathy, or ulceration, and 7,379 (2.1%) admissions had these categories recorded in any one of six diagnostic fields. These figures were generated by 3,159 and 4,751 patients, respectively. This represented a range of crude annual incidence of admission of between 1.9 and 2.9 per 1,000 people. Patients with diabetes accounted for 625 (15.4%) of primary admissions, a crude annual incidence of admission of 18.8 per 1,000. The age-standardized relative risk of admission for patients with diabetes to the nondiabetic population was 7.61 for men and 6.85 for women. The length of stay for patients with diabetes was almost twice that of the nondiabetic population (15.5 vs. 8.7 days). The relative risk of hospital mortality (diabetes vs. non-diabetes) was 2.83. Surgical procedures were carried out on 857 patients, 272 (31.2%) with diabetes. This represented an age-standardized relative risk of 31.19. The estimated cost of admissions for primary diagnoses in these categories over 4 years was 6,128,211 pounds ($9,743,855). Patients with diabetes accounted for 1,236,623 pounds ($1,966,230), an excess of 87% attributable to the diabetic state.

CONCLUSIONS

Diabetes is confirmed as a significant risk factor for peripheral vascular disease, infection, neuropathy, and ulceration. The severity of these disorders in terms of increased risk of hospital mortality, length of stay, and risk of surgical procedure is also demonstrated for those patients with diabetes.
Impact of Diabetes on Mortality After the First Myocardial Infarction
Authors: Miettinen Heikki , Lehto Seppo , Salomaa Veikko , Mähönen Markku , Niemelä Matti , Haffner Steven M , Pyörälä Kalevi , Tuomilehto Jaakko ,   The FINMONICA Myocardial Infarction Register Study Group
Published: March 2007

OBJECTIVE

To study diabetic and nondiabetic patients with their first myocardial infarction to determine overall 1-year mortality, out-of-hospital mortality, 28-day mortality of hospitalized patients, and 1-year mortality of 28-day survivors.

RESEARCH DESIGN AND METHODS

This study—based on the FINMONICA Myocardial Infarction Register, a part of the Finnish contribution to the WHO MONICA Project (World Health Organization Multinational Monitoring of Trends and Determinants of Cardiovascular Disease)—covered coronary heart disease (CHD) deaths and acute CHD events occurring during hospitalization among residents of Finland aged 25–64 years in three geographically defined areas. The study population comprised 620 diabetic and 3,445 nondiabetic patients who had their first myocardial infarction during the years 1988–1992.

RESULTS

The age- and area-adjusted mortality rates and hazard ratios (HRs) for diabetic versus nondiabetic patients (95% CI) were as follows: The 1-year mortality rate was 44.2% in diabetic men and 32.6% in nondiabetic men (HR, 1.38; 1.18−1.61) and 36.9% in diabetic women and 20.2% in nondiabetic women (HR, 1.86; 1.40−2.46); the out-of-hospital mortality rate was 28.3% in diabetic men and 22.4% in nondiabetic men (HR, 1.25; 1.03−1.52) and 10.4% in diabetic women and 11.0% in nondiabetic women (HR, 0.95; 0.58−1.54); the 28-day mortality rate of hospitalized patients was 14.4% in diabetic men and 8.8% in nondiabetic men (HR, 1.58; 1.15−2.18) and 21.7% in diabetic women and 7.8% in nondiabetic women (HR, 2.60; 1.71−3.95); and the 1-year mortality rate of 28-day survivors was 9.6% in diabetic men and 5.0% in nondiabetic men (HR, 1.97; 1.25−3.12) and 10.7% in diabetic women and 2.5% in nondiabetic women (HR, 4.17; 2.05−8.51).

CONCLUSIONS

The high mortality rate of diabetic patients after their first myocardial infarction and the high proportion of out-of-hospital deaths in this group imply that vigorous primary and secondary preventive measures should become an integral part of their medical care.
The Veterans Affairs Implantable Insulin Pump Study: Effect on cardiovascular risk factors
Authors: Duckworth William C , Saudek Christopher D , Giobbie-Hurder Anita , Henderson William G , Henry Robert R , Kelley David E , Edelman Steven V , Zieve Franklin J , Adler Robert A , Anderson James W , Anderson Robert J , Hamilton Bruce P , Donner Thomas W , Kirkman M Sue , Morgan Nancy A ,   The Department of Veterans Affairs Implantable Insulin Pump Study Group
Published: March 2007

OBJECTIVE

To determine whether implantable insulin pump (IIP) and multiple-dose insulin (MDI) therapy have different effects on cardiovascular risk factors in insulin-requiring patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

A randomized clinical trial was conducted at seven Veterans Affairs medical centers in 121 male patients with type 2 diabetes between the ages of 40 and 69 years receiving at least one injection of insulin per day and with HbAlc levels of ≥8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12 months, and free and total insulin levels were obtained at 0, 6, and 12 months. All medications being taken were recorded at each visit.

RESULTS

No difference in absolute blood pressure, neither systolic nor diastolic, was seen between patients receiving MDI or IIP therapy, but significantly more MDI patients required antihypertensive medications. When blood pressure was modeled against weight and time, IIP therapy was significantly better than MDI therapy for systolic blood pressure in patients with BMI <33 and for diastolic blood pressure in patients with BMI >34 kg/m2. Total cholesterol levels decreased in the overall sample, but IIP patients exhibited significantly higher levels than MDI patients. Triglyceride levels increased over time for both groups, with IIP patients having significantly higher levels than patients in the MDI group. BMI was a significant predictor of, and inversely proportional to, HDL cholesterol level. No difference in lipid-lowering drug therapy was seen between the two groups. Free insulin and insulin antibodies tended to decrease in the IIP group as compared with the MDI group. C-peptide levels decreased in both groups.

CONCLUSIONS

IIP therapy in insulinrequiring patients with type 2 diabetes has advantages over MDI therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Both therapies reduce total cholesterol and C-peptide levels
Role of Neuropathy and High Foot Pressures in Diabetic Foot Ulceration
Authors: Frykberg Robert G , Lavery Lawrence A , Pham Hau , Harvey Carolyn , Harkless Lawrence , Veves Aristidis
Published: March 2007

OBJECTIVE

High plantar foot pressures in association with peripheral neuropathy have been ascertained to be important risk factors for ulceration in the diabetic foot. Most studies investigating these parameters have been limited by their size and the homogeneity of study subjects. The objective of this study was therefore to ascertain the risk of ulceration associated with high foot pressures and peripheral neuropathy in a large and diverse diabetic population.

RESEARCH DESIGN AND METHODS

We studied a cross-sectional group of 251 diabetic patients of Caucasian (group C) (n = 121), black (group B) (n = 36), and Hispanic (group H) (n = 94) racial origins with an overall age of 58.5 ± 12.5 years (range 20–83). There was an equal distribution of men and women across the entire study population. All patients underwent a complete medical history and lower extremity evaluation for neuropathy and foot pressures. Neuropathic parameters were dichotomized (0/1) into two high-risk variables: patients with a vibration perception threshold (VPT) ≥25 V were categorized as HiVPT (n = 132) and those with Semmes-Weinstein monofilament tests ≥5.07 were classified as HiSWF (n = 190). The mean dynamic foot pressures of three footsteps were measured using the F-scan mat system with patients walking without shoes. Maximum plantar pressures were dichotomized into a high-pressure variable (Pmax6) indicating those subjects with pressures ≥6 kg/cm2 (n = 96). A total of 99 patients had a current or prior history of ulceration at baseline.

RESULTS

Joint mobility was significantly greater in the Hispanic cohort compared with the other groups at the first metatarsal-phalangeal joint (C 67 ± 23°, B 69 ± 23°, H 82 ± 23°, P = 0.000), while the subtalar joint mobility was reduced in the Caucasian group (C 21 ± 8°, B 26 ± 7°, H 27 ± 11°, P = 0.000). Maximum plantar foot pressures were significantly higher in the Caucasian group (C 6.7 ± 2.9 kg/cm2, B 5.7 ± 2.8 kg/cm2, H 4.4 ±1.9 kg/cm2 P = 0.000). Univariate logistic regression for Pmax6 on the history of ulceration yielded an odds ratio (OR) of 3.9 (P = 0.000). For HiVPT, the OR was 11.7 (P = 0.000), and for HiSWF, the OR was 9.6 (P = 0.000). Controlling for age, diabetes duration, sex, and race (all P < 0.05), multivariate logistic regression yielded the following significant associations with ulceration: Pmax6 (OR = 2.1, P = 0.002), HiVPT (OR = 4.4, P = 0.000), and HiSWF (OR = 4.1, P = 0.000).

CONCLUSIONS

We conclude that both high foot pressures (≥6 kg/cm2) and neuropathy are independently associated with ulceration in a diverse diabetic population, with the latter having the greater magnitude of effect. In black and Hispanic diabetic patients especially, joint mobility and plantar pressures are less predictive of ulceration than in Caucasians.
Oxidative Stress at Onset and in Early Stages of Type 1 Diabetes in Children and Adolescents
Authors: Domínguez Carmen , Ruiz Elena , Gussinye Miguel , Carrascosa Antonia
Published: March 2007

OBJECTIVE

In diabetes, the persistence of hyperglycemia has been reported to cause increased production of oxygen free radicals through glucose autooxidation and nonenzymatic glycation. The aim of this study was to determine whether oxidative cellular damage occurs at the clinical onset of diabetes and in later stages of the disease in young patients.

RESEARCH DESIGN AND METHODS

Indicative parameters of lipoperoxidation, protein oxidation, and changes in the status of antioxidant defense systems were evaluated in single blood samples from 54 diabetic children, adolescents, and young adults and 60 healthy age- and sex-matched control subjects.

RESULTS

Malondialdehyde and protein carbonyl group levels in plasma were progressively higher in diabetic children and adolescents than in control subjects (P < 0.0001). The highest erythrocyte superoxide dismutase (SOD) activity was found in diabetic children at onset of clinical diabetes. In diabetic adolescents, SOD was also significantly higher (P < 0.0001) than in control subjects. Erythrocyte glutathione peroxidase was significantly lower in diabetic children and adolescents compared with control subjects (P < 0.002). A significant decline in blood glutathione content at the recent onset of diabetes was found (P < 0.0001). Furthermore, our results demonstrated progressive glutathione depletion during diabetes evolution. The plasma α-tocopherol/total lipids ratio and β-carotene levels during diabetes development (P < 0.001) were low.

CONCLUSIONS

This cross-sectional study in young diabetic patients showed that systemic oxidative stress is present upon early onset of type 1 diabetes and is increased by early adulthood. Decreased antioxidant defenses may increase the susceptibility of diabetic patients to oxidative injury. Appropriate support for enhancing antioxidant supply in these young diabetic patients may help prevent clinical complications during the course of the disease.
Gestational diabetes: do lean young caucasian women need to be tested?
Authors: Moses R G , Moses J , Davis W S
Published: March 2007

OBJECTIVE: The American Diabetes Association has recommended that pregnant women with low-risk factors need not be tested for gestational diabetes mellitus (GDM). The aim of this study was to determine the prevalence of GDM in women with low-risk factors and to see if the pregnancy outcomes of women with GDM from a low-risk group were different from the outcomes of other women with GDM. RESEARCH DESION AND METHODS: Over an 18-month period, all pregnant women were offered a test for GDM using a 75-g glucose tolerance test at the beginning of the 3rd trimester. GDM was diagnosed if the 2-h glucose level was > or =8.0 mmol/l. The prevalence of GDM was determined in women with defined low-risk factors (Caucasian ethnic origin, age <25 years, and BMI <25 kg/m2). The pregnancy outcomes of women with GDM from a low-risk group were compared with those of other women with GDM. RESULTS: From a tested population of 2,907 women, 573 were identified as coming from a low-risk group. The prevalence of GDM in this low-risk group was 2.8%. The pregnancy outcomes of women with GDM from a low-risk group were no different from the pregnancy outcomes of other women with GDM, with respect to frequency of insulin use, units of insulin per day, morbidity, emergency caesarian section, and the percentage of both large- and small-for-gestational-age babies. In our population, if low-risk women were excluded, 80% of women would still require testing and nearly 10% of all cases of GDM would be missed. CONCLUSIONS: Women from a low-risk group have a 2.8% prevalence rate of GDM. The pregnancy outcomes of women with GDM from a low-risk group are similar to the outcomes of other women with GDM. Concerning the use of the 75-g glucose tolerance test in pregnancy, the recommendation not to test women from a low-risk group requires further evaluation in different populations before it can be endorsed.
Impaired glucose tolerance, type 2 diabetes, and carotid wall thickness: the Insulin Resistance Atherosclerosis Study.
Authors: Wagenknecht L E , D'Agostino R B , Haffner S M , Savage P J , Rewers M
Published: March 2007

OBJECTIVE: To assess whether people with impaired glucose tolerance (IGT) exhibit an increased risk of atherosclerosis as measured by the thickness of the carotid artery. RESEARCH DESIGN AND METHODS: We examined the relationship between glucose tolerance status and subclinical atherosclerosis in the Insulin Resistance Atherosclerosis Study (IRAS). The IRAS is an epidemiological study of 1,625 Hispanic, African-American, and white men and women, with approximately equal numbers of subjects with normal glucose tolerance (NGT), IGT, and type 2 diabetes as assessed by an oral glucose tolerance test. Half of those with diabetes were previously unaware of their condition and were defined as having new diabetes. Persons using insulin were excluded. The intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA) was measured as an index of subclinical atherosclerosis using B-mode ultrasonography. RESULTS: Adjusted for demographics and smoking, CCA-IMT increased most notably at the level of established diabetes (802, 822, 831, and 896 microm for NGT, IGT, new diabetes, and established diabetes, respectively). Adjustment for coronary heart disease (CHD) risk factors, which tended to worsen across glucose tolerance category, further minimized the slightly graded relationship. The relationship with the ICA-IMT was steeper and again suggested that the increased wall thickness is associated with diabetes, not with IGT. The relationship between glucose tolerance category and IMT was similar in men and women. CONCLUSIONS: We observed considerably greater IMT among persons with established diabetes but no significant increase in persons with IGT. These data suggest that the increased risk of CHD observed in persons with diabetes may largely develop after the onset of overt diabetes.
Differential effects of BMI on diabetes risk among black and white Americans.
Authors: Resnick H E , Valsania P , Halter J B , Lin X
Published: March 2007

OBJECTIVE: To determine whether the associations of BMI and fat distribution with diabetes risk are modified by race. RESEARCH DESIGN AND METHODS: Data from the National Health and Nutrition Examination Survey, Epidemiologic Follow-up Study (1971-1992), were used to investigate potential interactions of BMI and fat distribution with race. Incident diabetes was defined by self-report of physician-diagnosed diabetes, hospital and nursing home discharge records, and death certificates. RESULTS: Among the 1,531 black and 9,852 white subjects who were nondiabetic at baseline, 1,139 (10.0%) developed diabetes during 20 years of follow-up. Although the cumulative risk of diabetes increased with baseline BMI in all four race-sex groups, the sex-specific odds ratios (ORs) for black:white subjects decreased with increasing BMI. In particular, for BMI of 22 kg/m2, the OR of diabetes for black:white individuals was 1.87 and 1.76 (P < 0.01) for men and women, respectively; for BMI of 32 kg/m2, the OR decreased to 0.99 and 1.20 (NS) for men and women, respectively. Skinfold ratio was also associated with increased diabetes risk in all race-sex groups, but did not modify the association between race and diabetes. CONCLUSIONS: These findings suggest that the effect of BMI on diabetes risk is different for black and white Americans, with a larger risk for blacks than whites at low BMI and an equivalent risk for both groups at high BMI. A lower degree of visceral adiposity among blacks at higher BMI or a greater impact of visceral adiposity among blacks at low BMI may help explain the interaction of race and BMI on diabetes risk.
Determinants of the quality of life of patients with diabetes under intensified insulin therapy.
Authors: Rose M , Burkert U , Scholler G , Schirop T , Danzer G , Klapp B F
Published: March 2007

OBJECTIVE: The concept of quality of life (QOL) is understood as a multidimensional construct made up of physiological, psychological, and social aspects, but their particular weightings for the global QOL are rarely investigated. We examined 1) the general QOL of patients with diabetes, 2) the significance of the individual QOL aspects for the overall assessment of QOL, and 3) the modulating function of coping mechanism and particular personality traits. RESEARCH DESIGN AND METHODS: A total of 116 diabetes patients under intensified insulin therapy were studied, as were 107 patients with inflammatory bowel disease, 66 patients with chronic hepatitis C, and 229 students who served as control subjects. The examination was based on eight standardized QOL and personality questionnaires (354 items) and assessed by means of linear structural regression models (AMOS 3.6). RESULTS: The QOL of diabetes patients appears to be higher than the QOL of other chronically ill patients. Social, psychological, and physical aspects contribute to the overall QOL, although physical complaints receive a comparatively low weighting. Coping behavior and particular personality traits covary with all QOL aspects, giving these variables greater significance for the QOL than the existence of secondary illnesses. CONCLUSIONS: The hypothesis that the various factors involved in the multidimensional construct QOL receive different weightings was confirmed, making a simple summary score for the general QOL appear unjustifiable. In addition, all aspects that are commonly understood as parameters of QOL are influenced by external factors, such as coping behavior, based on individual personality characteristics.
Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes: a preliminary study.
Authors: Tütüncü N B , Bayraktar M , Varli K
Published: March 2007

OBJECTIVE: The present study has examined the effect of vitamin E, the principal modulator of free radical activity, on electrophysiological parameters in patients with diabetic peripheral sensorimotor polyneuropathy, matched for duration of disease and metabolic control. RESEARCH DESIGN AND METHODS: A total of 21 subjects with type 2 diabetes were enrolled in this double-blind randomized placebo-controlled study (vitamin E, 11 patients; placebo, 10 patients). Patients were randomly assigned to receive either 900 mg vitamin E or placebo for 6 months. The average dietary vitamin E consumption of the subjects was similar during the study. The main outcome measure was the electrophysiological tests assessing nerve conduction. Fasting plasma glucose, HbA1, postprandial plasma glucose, and electrophysiological parameters in the basal state and after 6 months of treatment were studied. RESULTS: Glycemic indexes did not show any significant changes during the study, whereas nerve conduction improved significantly in 2 of the 12 studied electrophysiological parameters after 6 months in patients on vitamin E supplementation. The changes in the electrophysiological parameters were obvious in the median motor nerve fibers and tibial motor nerve fibers. Nerve conduction velocity in the median motor nerve fibers (P = 0.0019) and tibial motor nerve distal latency (P = 0.0284) improved significantly after 6 months of vitamin E supplementation. CONCLUSIONS: This study shows that defective nerve conduction in diabetic subjects with mild-to-moderate peripheral neuropathy may be improved by pharmacological doses of vitamin E supplementation. Further studies with a larger number of patients for longer periods of time are needed.
Clinical and statistical evaluation of self-monitoring blood glucose meters.
Authors: Poirier J Y , Le Prieur N , Campion L , Guilhem I , Allannic H , Maugendre D
Published: March 2007

OBJECTIVE: Our objective was to compare statistical and clinical methods for the evaluation of five self-monitoring blood glucose (SMBG) meters. RESEARCH DESIGN AND METHODS: Two successive capillary blood glucose measurements were performed, and a simultaneous laboratory venous glucose measurement was used as the reference value. Accuracy was studied by comparing each of the two successive meter values with the reference value by 1) a Spearman's correlation test, 2) a Wilcoxon's paired test, 3) the percentage of values within the 10% interval of the reference value according to the American Diabetes Association consensus statement, and 4) the error grid analysis. RESULTS: The first two methods did not discriminate between the SMBG systems: r was >0.92 for the five meters, and a significant difference between the meter and reference values was found for all but one meter. The two other methods allowed classification of the devices into three groups according to their accuracy: good (two meters), acceptable (two meters), and unacceptable (one meter). These two methods gave consistent results and both had a good reproducibility, because the classification was similar for the two successive measurements. CONCLUSIONS: Both the Spearman's and Wilcoxon's paired tests, although commonly used, are inappropriate to evaluate SMBG systems. The percentage of SMBG values within the +/-10% interval and the error grid analysis are more accurate, because they consistently classified the five glucose meters tested in our study with a high degree of reproducibility.
Effects of autonomic neuropathy on counterregulation and awareness of hypoglycemia in type 1 diabetic patients.
Authors: Meyer C , Grossmann R , Mitrakou A , Mahler R , Veneman T , Gerich J , Bretzel R G
Published: March 2007

OBJECTIVE: The recent EURODIAB Study has identified autonomic neuropathy as an independent risk factor for severe hypoglycemia in patients with type 1 diabetes. We tested the hypothesis that counterregulatory catecholamine responses and awareness of hypoglycemia are impaired to a greater extent in type 1 diabetic patients with autonomic neuropathy (AN+) than in those without autonomic neuropathy (AN-). RESEARCH DESIGN AND METHODS: We studied 22 type 1 diabetic patients (8 AN+, 14 AN-) matched for age, duration of diabetes, glycemic control, and history of hypoglycemic episodes. We also studied 33 nondiabetic control subjects using the stepped hypoglycemic clamp technique and determined glycemic thresholds and magnitudes of counterregulatory hormone responses and of hypoglycemia symptoms. RESULTS: Both groups of diabetic patients had reduced awareness of hypoglycemia as evidenced by an elevated glycemic threshold for autonomic symptoms > or =2 SD above normal but neither the magnitude nor thresholds for symptoms differed in AN+ patients and AN-patients. Both groups also had impaired glucagon, epinephrine, norepinephrine, growth hormone and cortisol responses to hypoglycemia. However, in AN+ patients compared with AN-patients, magnitudes of epinephrine and norepinephrine responses (194+/-49 vs. 784+/-206 pmol/l, P < 0.007, and 316+/-56 vs. 610+/-87 pmol/l, P < 0.02, respectively) and epinephrine and norepinephrine glycemic thresholds (2.33+/- 0.10 vs. 2.82+/-0.10 mmol/l, P < 0.009 and 2.34+/-0.06 vs. 2.79+/-0.10 mmol/l, P < 0.008, respectively) were impaired to a greater extent. This was associated with a 50% greater requirement of exogenous glucose to prevent more severe hypoglycemia during the 2.3 mmol/l glycemic plateau (P < 0.002). No differences were observed between other counterregulatory hormone responses in AN+ and AN- patients. CONCLUSIONS: We conclude that in patients with type 1 diabetes, autonomic neuropathy further reduces counterregulatory catecholamine responses. Since this should increase the risk for severe hypoglycemia, one might consider safer therapeutic goals in these patients.
Use of immunoglobulin A-antiendomysial antibody to screen for celiac disease in North American children with type 1 diabetes.
Authors: Fraser-Reynolds K A , Butzner J D , Stephure D K , Trussell R A , Scott R B
Published: March 2007

OBJECTIVE: Our objective was to determine if a serological marker, the immunoglobulin A antiendomysial antibody (IgA-EMA), can be used to screen for celiac disease in North American children with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects included 236 diabetes clinic patients and 56 gastrointestinal clinic patients who underwent intestinal biopsy for suspected malabsorption. Total IgA and IgA-EMA assays were performed. Diabetic patients who were positive for IgA-EMA were asked to undergo biopsy. RESULTS: Of 236 diabetic patients tested, none were IgA deficient and 19 were positive for IgA-EMA (8%). Of 17 patients biopsied, 12 had celiac disease and 3 were symptomatic. The estimated prevalence of celiac disease was 5.1%, consistent with data from European diabetic clinics. Of the 56 gastrointestinal clinic patients, the 3 who were IgA-EMA positive had biopsies diagnostic of celiac disease. Three were found to be IgA deficient, one of whom had celiac disease. Of the 50 IgA-sufficient and IgA-EMA-negative patients, 1 had celiac disease and 49 did not. The IgA-EMA test had a sensitivity of 94% and a specificity of 91% for IgA-sufficient biopsied patients. CONCLUSIONS: IgA-EMA is an appropriate tool for demonstrating an increased prevalence of celiac disease in a North American pediatric diabetic population. Positive testing should be confirmed by intestinal biopsy, and false-positive results require serial follow-up. Symptomatic children require biopsy regardless of their IgA-EMA status.
Efficacy and Safety of Acarbose in Insulin-Treated Patients With Type 2 Diabetes
Authors: Kelley David E , Bidot Pascual , Freedman Zachary , Haag Burritt , Podlecki David , Rendell Marc , Schimel David , Weiss Stuart , Taylor Terry , Krol Alice , Magner James
Published: March 2007

OBJECTIVE

To demonstrate the efficacy, tolerability, and safety of acarbose compared with placebo in patients with type 2 diabetes inadequately controlled with diet and insulin.

RESEARCH DESIGN AND METHODS

A multicenter randomized double-blind placebo-controlled parallel-group comparison study was conducted. The trial was 26 weeks with a 2-week screening period and a 24-week period of treatment with acarbose or placebo, with forced titration from 25 mg t.i.d. to 50 mg t.i.d. after 4 weeks, and titration of 50 mg t.i.d. to 100 mg t.i.d. after 12 weeks based on glucose control. The dosage of insulin was toremain stable. The primary efficacy variable was mean change from baseline in HbA1c, and secondary efficacy variables included mean changes in fasting and postprandial plasma glucose and triglyceride levels.

RESULTS

The addition of acarbose to the treatment of patients receiving background insulin and diet therapy resulted in a statistically significant reduction in mean HbA1c of 0.69% compared with placebo. Therewere statistically significant reductions in postprandial plasma glucose and glucose area under the curve, and in postprandial serum triglyceride levels in the acarbose-treated patients. Gastrointestinal side effects were more frequently reported in the acarbose-treated patients. There were no significant differences in hypoglycemic events or liver transaminase elevations between groups.

CONCLUSIONS

This study demonstrated that the addition of acarbose to patients with type 2 diabetes who are inadequately controlled with insulin and diet is safe and generally well tolerated and that it significantly lowers HbA1c and postprandial glucose levels.
Hyperfiltration in African-American Patients With Type 2 Diabetes: Cross-sectional and longitudinal data
Authors: Chaiken Rochelle L , Eckert-Norton Margaret , Bard Mara , Banerji Mary Ann , Palmisano Joanne , Sachimechi Isaac , Lebovitz Harold E
Published: March 2007

OBJECTIVE

Hyperfiltration may play a role in the development of diabetic nephropathy. African-American patients with diabetes have more than a fourfold increase in end-stage renal disease. The purpose of this study is to evaluate the impact of hyperfiltration on renal function in African-American patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

Renal function of 194 African-American patients with diagnosed type 2 diabetes from 1 month to 36 years was assessed by studies of isotopic glomerular filtration rate (GFR), serum creatinine, creatinine clearance, and 24-h urinary albumin excretion rates. Thirty-four patients with a duration of diagnosed type 2 diabetes from 1 month to 10 years were found to have hyperfiltration (GFR ≥140 ml · min−1 · 1.73 min2). Fifteen of these patients received longitudinal follow-up of renal function for as long as 15 years after the initial study.

RESULTS

Hyperfiltration is present in 15 (36%) of 42 patients whose duration of diagnosed type 2 diabetes is <1 year, and it persists for up to 10 years in 14–20% of patients with diagnosed type 2 diabetes. Patients with hyperfiltration are younger than their counterparts without hyperfiltration when matched for duration of diagnosed diabetes. When followed over time, those patients with hyperfiltration were not more likely to develop impaired renal function as measured by GFR or creatinine clearance.

CONCLUSIONS

Hyperfiltration does not identify patients at risk for deterioration in renal function
High Serum Lipoprotein(a) Levels in Korean Type 2 Diabetic Patients With Proliferative Diabetic Retinopathy
Authors: Kim Chul-Hee , Park Hyung-Joo , Park Joong-Yeol , Hong Sung-Kwan , Yoon Young-Hee , Lee Ki-Up
Published: March 2007

OBJECTIVE

To examine the possible association between serum lipoprotein(a) [Lp(a)] concentration and proliferative diabetic retinopathy (PDR) in Korean patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

A total of 412 Korean outpatients with type 2 diabetes were examined. Diabetic retinopathy was determined by an ophthalmologist using fundoscopic examination. Serum Lp(a) levels were measured by two-site sandwich enzymelinked immunosorbent assay.

RESULTS

The patients with PDR had higher serum Lp(a) levels than those with no diabetic retinopathy or with nonproliferative diabetic retinopathy (NPDR). Multiple logistic regression analysis showed that high serum Lp(a) levels and the presence of diabetic nephropathy were independent variables having a statistically significant association with PDR.

CONCLUSIONS

Korean type 2 diabetic patients with PDR had higher serum Lp(a) levels versus those with no diabetic retinopathy or with NPDR. Although these results suggest that Lp(a) might play a role in the occlusion of retinal capillaries leading to PDR, further prospective studies are required to prove the causal relationship.
Estimation of the Glomerular Filtration Rate in NIDDM Patients From Plasma Creatinine Concentration After Cimetidine Administration
Authors: Kemperman Frits AW , Silberbusch Joseph , Slaats Eduard H , Prins Ariël M , Weber Joop A , Krediet Raymond T , Arisz Lambertus
Published: March 2007

OBJECTIVE

Glomerular filtration rate (GFR) can be estimated in patients with renal disease from plasma creatinine concentration, age, sex, and body weight according to the formula of Cockcroft and Gault. The hypothesis that this method can be improved when tubular secretion of creatinine is inhibited by cimetidine was studied in NIDDM patients.

RESEARCH DESIGN AND METHODS

In 30 outpatients with NIDDM and normo-(n = 10), micro- (n = 9), or macroalbuminuria (n = 11), GFR was measured as the urinary clearance during continuous infusion of 125I-labeled iothalamate. Plasma creatinine concentration was analyzed with an enzymatic assay before and after 800 mg t.i.d. oral cimetidine was given during a 24-h period.

RESULTS

Plasma creatinine rose in all patients after cimetidine administration and, as a consequence, the clearance calculated with the Cockcroft-Gault formula fell. The ratio of this formula and GFR decreased from 1.16 ± 0.20 to 0.97 ± 0.16 (means ± SD). This ratio tended to be smaller in the normo- (0.93) than in the micro- (0.98) and macroalbuminuric (1.00) groups. Also, 20 patients with a BMI < 30 kg/m2 had a smaller ratio than those with a BMI > 30 kg/m2 (0.92 vs. 1.07; P < 0.05). Bland and Altman analysis showed a difference of the Cockcroft-Gault formula and GFR of 12.0 ± 17.4 ml · min−1 · (1.73 m2)−1, which decreased to −3.8 ± 14.8 ml · min−1 · (1.73 m2)−1. The same analysis of 24-h creatinine clearance with urine collection and GFR showed larger standard deviations.

CONCLUSIONS

GFR can be estimated in an acceptable way from plasma creatinine concentration after cimetidine administration in outpatients with NIDDM. Despite a nonsignificant underestimation in normoalbuminuric and overestimation in overweighted patients, this method is superior to 24-h creatinine clearance with outpatient urine collection.
Hospitalization and Mortality of Diabetes in Older Adults: A 3-year prospective study
Authors: Rosenthal Mark J , Fajardo Mercedes , Gilmore Stephanie , Morley John E , Naliboff Bruce D
Published: March 2007

OBJECTIVE

In light of increased fatality from acute events and the increased frequency of chronic complications, life expectancy might well be shortened in older patients with diabetes. The current studies investigated factors affecting the likelihood of dying or being hospitalized in older patients with diabetes.

RESEARCH DESIGN AND METHODS

A total of 135 older patients with diabetes were followed for 3 years after predictive factors were evaluated and compared with a cohort of patients without diabetes.

RESULTS

Mortality was only 3,250 per 100,000 patient-years, similar to that for patients without diabetes, but the frequency of hospitalizations was more than twice as high in patients with diabetes. Five factors predicted hospitalization and death. Of these, the geriatric depression score was the best predictor of these poor outcomes.

CONCLUSIONS

Older patients with diabetes were hospitalized more often than those without diabetes, but mortality was similar. Dysphoria is a major predictor of poor outcomes in older patients with diabetes.
Unrecognized Diabetes Among Hospitalized Patients
Authors: Levetan Claresa S , Passaro Maureen , Jablonski Kathleen , Kass Mary , Ratner Robert E
Published: March 2007

OBJECTIVE

To evaluate the hospital care rendered to hyperglycemic individuals who did not have a diagnosis of diabetes before admission.

RESEARCH DESIGN AND METHODS

A total of 1,034 consecutively hospitalized adult patients at a 750-bed inner-city teaching hospital were evaluated. Patients with one or more plasma glucose values >200 mg/dl were identified by the laboratory data system on a daily basis. Patients without a diagnosis of diabetes at the time of admission were evaluated to determine if and how physicians addressed the hyperglycemia, whether a new diagnosis of diabetes was made during admission, and whether follow-up was planned to address the hyperglycemia.

RESULTS

After excluding patients who were admitted for a primary diagnosis of diabetes, 37.5% of all hyperglycemic medical patients and 33% of hyperglycemic surgical patients were without a diagnosis of diabetes at the time of admission. These patients had a mean peak glucose of 299 mg/dl, and 66% had two or more elevated values during their hospitalization. Fifty-four percent received insulin therapy, and 59% received bedside glucose monitoring, yet 66% of daily patient progress notes failed to comment on the presence of hyperglycemia or diabetes. Diabetes was documented in only three patients (7.3%) as a possible diagnosis in the daily progress notes.

CONCLUSIONS

Despite marked hyperglycemia, most medical records made no reference to the possibility of unrecognized diabetes. Given the average delay of a decade between the onset and diagnosis of type 2 diabetes, further evaluation of hyperglycemic hospitalized patients may present an important opportunity for earlier detection and the initiation of therapy.
Insulin Secretion in Normal Glucose-Tolerant Relatives of Type 2 Diabetic Subjects: Assessments using hyperglycemic glucose clamps and oral glucose tolerance tests
Authors: van Haeften Timon W , Dubbeldam Suzanne , Zonderland Maria L , Erkelens D Willem
Published: March 2007

OBJECTIVE

To assess insulin secretion in normal glucose-tolerant Caucasian first-degree relatives of type 2 diabetes subjects and in matched normal glucose-tolerant control subjects and to compare insulin secretion as assessed using a hyperglycemic glucose clamp with insulin secretion as assessed using an oral glucose tolerance test (OGTT).

RESEARCH DESIGN AND METHODS

Twenty-one first-degree relatives of type 2 diabetic subjects and 21 control subjects without a family history of type 2 diabetes, who were matched for sex, age, BM1, waist-to-hip ratio, and aerobic capacity, underwent a hyperglycemic glucose clamp (10 mmol/1, 180 min). An OGTT (75 g glucose in 300 ml water) was also performed.

RESULTS

First-phase insulin release (plasma insulin, 0–10 min) was not different (multiple analysis of variance [MANOVA]: F = 2.63, P = 0.11). Second-phase insulin release was lower (MANOVA: F = 4.18, P = 0.047). Separate analyses of variance showed decreased plasma insulin levels from 120 min onward (all P < 0.05), decreasing to geometric mean (95% CI) levels of 330 (270–402) and 462 (366–582) pmol/1 at 180 min in relatives and control subjects, respectively. The insulin sensitivity index (ISI) as assessed using a hyperglycemic clamp was not different between the two groups. Mean ± SE ISI during the 3rd hour was 27.5 ± 2.2 and 30.5 ± 3.0 μg · kg−1 · min−1 · pmol−1 · l−1 in relatives and control subjects, respectively (P > 0.20). At 90 min after the OGTT, log plasma insulin levels correlated significantly with secondphase insulin release as assessed using the hyperglycemic glucose clamp.

CONCLUSIONS

Normal glucose-tolerant first-degree relatives of type 2 diabetic subjects have a decreased second-phase insulin release, compared with matched control subjects. After an OGTT, 90-min values of log plasma insulin and 90-min values of the ratio of log plasma insulin to blood glucose may be good indicators of insulin secretory properties in normal glucose-tolerant family members of type 2 diabetic subjects.
Effects of Glycemic Control on Protective Responses Against Hypoglycemia in Type 2 Diabetes
Authors: Korzon-Burakowska Anna , Hopkins David , Matyka Krystyna , Lomas Jill , Pernet Andrew , Macdonald IAN , Amiel Stephanie
Published: March 2007

OBJECTIVE

To determine the effects of glycemic control on the counterregulatory responses to hypoglycemia in type 2 diabetes.

RESEARCH DESIGN AND METHODS

Seven poorly controlled type 2 diabetes patients (mean HbA1c, 11.3 ± 1.1%) were studied by stepped hyperinsulinemic hypoglycemic clamp (nadir, 2.4 mmol/1) before and after improving glycemic control with insulin treatment. Counterregulatory hormones, symptoms, and four-choice reaction time were measured at each glucose plateau.

RESULTS

In patients with poorly controlled type 2 diabetes, counterregulatory hormone responses began at higher plasma glucose levels than did those in healthy subjects (epinephrine, 4.4 ± 0.2 vs. 3.7 ± 0.2 mmol/1, P = 0.011). After significant improvement in glycemic control (mean HbA1c, 8.1 ± 0.9%, P < 0.001) was achieved without severe hypoglycemia, hormonal responses started at much lower plasma glucose levels (e.g., epinephrine, 3.5 ± 0.3 mmol/1, P = 0.005) and were significantly reduced in magnitude (e.g., area under epinephrine response curve, 306 ± 93 vs. 690 ± 107 nmol · min−1 · l−1, P = 0.012). This was accompanied by a change in the plasma glucose threshold at which hypoglycemic symptoms first developed from 3.6 ± 0.2 to 3.0 ± 0.2 mmol/1 (P = 0.019). In contrast, the plasma glucose threshold at which four-choice reaction time deteriorated did not change significantly (3.1 ±0.1 vs. 2.9 ± 0.1 mmol/1, P = 0.125).

CONCLUSIONS

Counterregulatory responses begin at normoglycemia in poorly controlled type 2 diabetes. Improving glycemic control with insulin therapy normalizes hormonal responses but lowers the plasma glucose levels at which hypoglycemic symptoms develop to levels associated with impairment of four-choice reaction time, a marker of cognitive function. This process potentially increases the risk of severe hypoglycemia, but to a lesser extent than occurs in type 1 disease.
Economic Consequences of Diabetes Mellitus in the U.S. in 1997
Authors:   American Diabetes Association
Published: March 2007

OBJECTIVE

Diabetes is a significant public health problem resulting in substantial morbidity and mortality. The objectives of this study were 1) to determine the direct medical and indirect costs attributable to diabetes and 2) to calculate total and per capita expenditures of people with and without diabetes.

RESEARCH DESIGN AND METHODS

Direct medical and indirect expenditures attributable to diabetes in 1997 were estimated at $98 billion. Medical expenditures for the treatment of diabetes were estimated for all individuals in the U.S. in 1997 by age-group, sex, race, type of condition, and site of service. Productivity costs due to disability and premature mortality were also estimated for selected patient cohorts. Etiological fractions based on national health care survey data and published literature were used to estimate the proportion of health service utilization and mortality associated with diabetes-related chronic complications and general medical conditions.

RESULTS

Direct medical expenditures attributable to diabetes in 1997 totaled $44.1 billion and comprised $7.7 billion for diabetes and acute glycemic care, $11.8 billion due to the excess prevalence of related chronic complications, and $24.6 billion due to the excess prevalence of general medical conditions. The majority of attributable expenditures were for inpatient care (62%), followed by outpatient services (25%) and nursing home care (13%). Two-thirds of all medical costs for diabetes were borne by elderly people. Attributable indirect costs totaled $54.1 billion and comprised $17.0 billion resulting from premature mortality and $37.1 billion from disability. Total medical expenditures incurred by people with diabetes totaled $77.7 billion or $10,071 per capita, compared with $2,669 for people without diabetes.

CONCLUSIONS

The economic burden of diabetes mellitus in the U.S. is enormous. Medical innovations that can delay the onset and slow the progression of diabetes have tremendous potential to mitigate the associated clinical and cost repercussions.