bluuebunny/crossref_metadata_2025 huggingface dataset:
Gestational Diabetes and the Incidence of Type 2 Diabetes
Authors: Kim Catherine , Newton Katherine M. , Knopp Robert H.
Published: March 2007

OBJECTIVE—To examine factors associated with variation in the risk for type 2 diabetes in women with prior gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS—We conducted a systematic literature review of articles published between January 1965 and August 2001, in which subjects underwent testing for GDM and then testing for type 2 diabetes after delivery. We abstracted diagnostic criteria for GDM and type 2 diabetes, cumulative incidence of type 2 diabetes, and factors that predicted incidence of type 2 diabetes.

RESULTS—A total of 28 studies were examined. After the index pregnancy, the cumulative incidence of diabetes ranged from 2.6% to over 70% in studies that examined women 6 weeks postpartum to 28 years postpartum. Differences in rates of progression between ethnic groups was reduced by adjustment for various lengths of follow-up and testing rates, so that women appeared to progress to type 2 diabetes at similar rates after a diagnosis of GDM. Cumulative incidence of type 2 diabetes increased markedly in the first 5 years after delivery and appeared to plateau after 10 years. An elevated fasting glucose level during pregnancy was the risk factor most commonly associated with future risk of type 2 diabetes.

CONCLUSIONS—Conversion of GDM to type 2 diabetes varies with the length of follow-up and cohort retention. Adjustment for these differences reveals rapid increases in the cumulative incidence occurring in the first 5 years after delivery for different racial groups. Targeting women with elevated fasting glucose levels during pregnancy may prove to have the greatest effect for the effort required.
Diabetes in Employer-Sponsored Health Insurance
Authors: Peele Pamela B. , Lave Judith R. , Songer Thomas J.
Published: March 2007

OBJECTIVE—To examine medical and mental health care expenditures for large numbers of individuals with diabetes enrolled in employment-sponsored insurance plans.

RESEARCH DESIGN AND METHODS—Health insurance billing data for ∼1.3 million individuals enrolled in health insurance plans sponsored by 862 large self-insured employers nationwide were used to examine employer expenditures and consumer out-of-pocket payments for 20,937 people identified with diabetes. These expenditures were compared with expenditures for individuals with other chronic illnesses. Main outcome measures were covered charges, insurance plan reimbursements, and estimated consumer out-of-pocket payments for both medical and mental health services.

RESULTS—A total of 1.7% of enrollees were identified as having diabetes and ∼11% of those used at least one mental health service during 1996. Health care expenditures were three times higher for those with diabetes compared with all health care consumers in these insurance plans, but when compared with individuals with other chronic illnesses such as heart disease, HIV/AIDS, cancer, and asthma, those with diabetes were not more expensive for employers’ insurance plans. Diabetes accounts for 6.5% of total health plan expenditures.

CONCLUSIONS—Diabetes is not more expensive for either consumers or their employer-sponsored insurance plans than other chronic illnesses.
A Multivariate Logistic Regression Equation to Screen for Diabetes
Authors: Tabaei Bahman P. , Herman William H.
Published: March 2007

OBJECTIVE—To develop and validate an empirical equation to screen for diabetes.

RESEARCH DESIGN AND METHODS—A predictive equation was developed using multiple logistic regression analysis and data collected from 1,032 Egyptian subjects with no history of diabetes. The equation incorporated age, sex, BMI, postprandial time (self-reported number of hours since last food or drink other than water), and random capillary plasma glucose as independent covariates for prediction of undiagnosed diabetes. These covariates were based on a fasting plasma glucose level ≥126 mg/dl and/or a plasma glucose level 2 h after a 75-g oral glucose load ≥200 mg/dl. The equation was validated using data collected from an independent sample of 1,065 American subjects. Its performance was also compared with that of recommended and proposed static plasma glucose cut points for diabetes screening.

RESULTS—The predictive equation was calculated with the following logistic regression parameters: P = 1/(1 − e−x), where x = −10.0382 + [0.0331 (age in years) + 0.0308 (random plasma glucose in mg/dl) + 0.2500 (postprandial time assessed as 0 to ≥8 h) + 0.5620 (if female) + 0.0346 (BMI)]. The cut point for the prediction of previously undiagnosed diabetes was defined as a probability value ≥0.20. The equation’s sensitivity was 65%, specificity 96%, and positive predictive value (PPV) 67%. When applied to a new sample, the equation’s sensitivity was 62%, specificity 96%, and PPV 63%.

CONCLUSIONS—This multivariate logistic equation improves on currently recommended methods of screening for undiagnosed diabetes and can be easily implemented in a inexpensive handheld programmable calculator to predict previously undiagnosed diabetes.
Proteinuria as a Predictor of Total Plasma Homocysteine Levels in Type 2 Diabetic Nephropathy
Authors: Friedman Allon N. , Hunsicker Lawrence G. , Selhub Jacob , Bostom Andrew G. ,   The Collaborative Study Group
Published: March 2007

OBJECTIVE—Patients with diabetes who manifest proteinuria are at increased risk for cardiovascular events. Some studies suggest that proteinuria exerts its cardiovascular effects at least partly through a positive association with total plasma homocysteine (tHcy). Modestly sized but better designed contrary studies find no such link through a limited range of serum creatinine and proteinuria. We tested the hypothesis that proteinuria independently predicts tHcy levels in a larger cohort of type 2 diabetic patients with nephropathy throughout a much broader range of kidney disease and proteinuria.

RESEARCH DESIGN AND METHODS—Baseline data for the cross-sectional study were obtained from 717 patients enrolled in the multicenter Irbesartan Diabetic Nephropathy Trial. All subjects had type 2 diabetes, hypertension, and proteinuria and were between 29 and 78 years of age. Data included age, sex, BMI, serum creatinine and albumin, LDL and HDL cholesterol, triglyceride, proteinuria and albuminuria, plasma folate, B12, and pyridoxal 5′-phosphate (PLP) (the active form of B6), HbA1c, and tHcy levels. Unadjusted and multivariable models were used in the analysis.

RESULTS—Crude analyses revealed significant associations between tHcy and age (r = 0.074; P = 0.008), creatinine (r = 0.414; P < 0.001), PLP (r = −0.105; P = 0.021), B12 (r = −0.216; P < 0.001), folate (r = −0.241; P < 0.001), and HbA1c (r = −0.119; P = 0.003), with serum albumin approaching significance (r = 0.055; P = 0.072). Only serum creatinine, plasma folate, B12, serum albumin, sex, HbA1c, and age were independent predictors of tHcy after controlling for all other variables.

CONCLUSIONS—By finding no independent correlation between proteinuria (or albuminuria) and tHcy levels, this study improves the external validity of previous negative findings. Therefore, it is unlikely that the observed positive association between proteinuria and cardiovascular disease is directly related to hyperhomocysteinemia.
Increased Risk of Childhood Type 1 Diabetes in Children Born After 1985
Authors: Svensson Jannet , Carstensen Bendix , Mølbak AnneGrete , Christau Bjørn , Mortensen Henrik B. , Nerup Jørn , Borch-Johnsen Knut ,   the Danish Study Group of Diabetes in Childhood (DSBD)
Published: March 2007

OBJECTIVE—The incidence rate of childhood type 1 diabetes is thought to be increasing; however, Danish studies have not confirmed this. Using a national diabetes register initiated in 1996 and two previous regional incidence studies, we studied the age-specific incidence of type 1 diabetes over 30 years. Here, we describe the incidence rates of type 1 diabetes in Danish children from 1996 to 2000 and evaluate trends in age-specific incidence rates from 1970 to 2000.

RESEARCH DESIGN AND METHODS—A nationwide registration of all newly diagnosed cases of type 1 diabetes among children under the age of 15 years was established in Denmark in 1996. Incidence rates of type 1 diabetes in Denmark were obtained from this register. Age-specific incidence rates were compared with data collected from 1970 to 1976 and from 1980 to 1984, both population-based studies using existing national routine registration of hospitalizations within the survey areas. Population data were obtained from Statistics Denmark.

RESULTS—During the study period, 1,421 Danish children developed type 1 diabetes before the age of 15 years. The incidence rates by age-groups were: 12.7, 19.4, and 26.3 for the 0–4, 5–9, and 10–14 years age-groups, respectively, and 19.5 for the 0–14 years age-group per 100,000 in the period 1996–2000. An age-period-cohort analysis showed a modest drift effect (yearly increase) of 1.2% (0.7–1.8) from 1970 to 2000, and a significant birth cohort effect with an increased risk for children born after 1985 was observed.

CONCLUSIONS—The incidence rate of type 1 diabetes is rising in children living in Denmark. The steep increase in the youngest age-group was explained by the increased risk for cohorts born at the beginning of the 1980s.
The Prevalence of the HNF-1α G319S Mutation in Canadian Aboriginal Youth With Type 2 Diabetes
Authors: Sellers Elizabeth A.C. , Triggs-Raine Barbara , Rockman-Greenberg Cheryl , Dean Heather J.
Published: March 2007

OBJECTIVE—To investigate the prevalence of the unique HNF-1α G319S mutation in a population of aboriginal youth with type 2 diabetes and to describe the relationship between clinical and historical characteristics and the presence or absence of the HNF-1α G319S mutation.

RESEARCH DESIGN AND METHODS—Participating youth were genotyped for the G319S mutation of the HNF-1α gene. Clinical, laboratory, and historical data were collected via chart review (blinded to genotype results). Comparison data were derived from another study involving young nondiabetic pregnant aboriginal women.

RESULTS—A total of 51 youth seen sequentially in a type 2 diabetes clinic participated in this study. Of these, 21 (41.2%) had at least one copy of the mutant allele. The allele frequency in the study population was 0.29 (95% CI 0.20–0.38), which was significantly different from the allele frequency of 0.13 in the comparison population (χ2 = 6.78, P = 0.009). The frequency of the homozygous mutation (S319/S319) was 0.18. Mean BMI was significantly lower (P = 0.002), mean HbA1c was significantly higher (P = 0.02), and acanthosis nigricans was significantly less frequent (P = 0.004) in those with the mutation compared with the wild type. Mean insulin levels were lower and insulin sensitivity (assessed by homeostasis model assessment [HOMA]) was greater in the homozygote group compared with the wild-type group (P = 0.002 and P = 0.0007, respectively). A dose-dependent gradient was observed for these characteristics.

CONCLUSIONS—These data support the association between the HNF-1α G319S mutation and early-onset type 2 diabetes in this population. Those with the mutation lacked clinical characteristics of insulin resistance (e.g., obesity and acanthosis nigricans) and had lower insulin levels, suggesting that an insulin-secretory and/or -production defect plays an important role in the development of diabetes in this group. Further investigation of the pathophysiology of the S319 homo- and heterozygote is needed because it may impact treatment and/or prevention of this disease.
Comparison of Insulin Aspart With Buffered Regular Insulin and Insulin Lispro in Continuous Subcutaneous Insulin Infusion
Authors: Bode Bruce , Weinstein Richard , Bell David , McGill Janet , Nadeau Daniel , Raskin Philip , Davidson Jaime , Henry Robert , Huang Won-Chin , Reinhardt Rickey R.
Published: March 2007

OBJECTIVE—To compare the safety and efficacy of insulin aspart (IAsp), buffered regular insulin (BR), and insulin lispro administered by continuous subcutaneous insulin infusion (CSII) in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—After completing a 4-week run-in period with BR, 146 adult patients with type 1 diabetes (with pretrial CSII experience) were randomly assigned (2:2:1) to CSII treatment with IAsp, BR, or lispro for 16 weeks in a multicenter, open-label, randomized, parallel-group study. Bolus insulin doses were administered 30 min before meals (BR) or immediately before meals (IAsp or lispro).

RESULTS—Treatment groups had similar baseline HbA1c (7.3% ±0.7 for IAsp, 7.5% ±0.8 for BR, and 7.3% ±0.7 for lispro). After 16 weeks of treatment, HbA1c values were relatively unchanged from baseline, and the mean changes in baseline HbA1c values were not significantly different between the three groups (0.00 ±0.51, 0.15 ±0.63, and 0.18 ±0.84 for the IAsp, BR, and lispro groups, respectively). The rates of hypoglycemic episodes (blood glucose <50 mg/dl) per patient per month were similar (3.7, 4.8, and 4.4 for the IAsp, BR, and lispro groups, respectively). Clogs/blockages in pumps or infusion sets were infrequent; most subjects (76, 83, and 75% in the IAsp, BR, and lispro groups, respectively) had ≤1 clog or blockage per 4 weeks during the trial.

CONCLUSIONS—Insulin aspart in CSII was as efficacious and well tolerated as BR and lispro and is a suitable insulin for continuous subcutaneous insulin infusion using external pumps.
Effect of a Chicken-Based Diet on Renal Function and Lipid Profile in Patients With Type 2 Diabetes
Authors: Gross Jorge L. , Zelmanovitz Themis , Moulin Cileide C. , De Mello Vanessa , Perassolo Magda , Leitão Cristiane , Hoefel Alice , Paggi Alexandre , Azevedo Mirela J.
Published: March 2007

OBJECTIVE—To assess the effect of replacing red meat with chicken in the usual diet and the effect of a low-protein diet on glomerular filtration rate (GFR), urinary albumin excretion rate (UAER), and lipid levels in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A randomized, crossover, controlled trial was conducted with 28 patients with type 2 diabetes (seven women; mean age 58.1 years): 15 patients were normoalbuminuric (UAER <20 μg/min), and 13 patients were microalbuminuric (UAER 20–200 μg/min). A chicken-based diet (red meat replaced with chicken) and a low-protein diet were compared with the patients’ usual diet. Patients followed each diet for 4 weeks with a 4-week washout period between. GFR (51Cr-EDTA single-injection technique), 24-h UAER (immunoturbidimetry), apolipoprotein B, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were measured after each diet.

RESULTS—Normoalbuminuric and microalbuminuric patients with diabetes were analyzed separately. In normoalbuminuric patients, GFR after the chicken (101.3 ± 22.9 ml · min−1 · 1.73 m−2) and low-protein diets (93.8 ± 20.5 ml · min−1 · m−2) was lower than after the usual diet (113.4 ± 31.4 ml · min−1 · 1.73 m−2; P < 0.05). In microalbuminuric patients, apolipoprotein B levels were lower after the chicken (113.5 ± 36.0 mg/dl) and low-protein diets (103.5 ± 40.1 mg/dl) than after the usual diet (134.3 ± 30.7 mg/dl; P < 0.05). Only the chicken diet reduced UAER (median 34.3 μg/min) compared with the low-protein (median 52.3 μg/min) and usual (median 63.8 μg/min) diets (P < 0.05). Glycemic control and blood pressure did not change after the diets.

CONCLUSIONS—A normoproteic diet with chicken as the only source of meat may represent an alternative strategy for treatment of patients with type 2 diabetes and microalbuminuria.
Detection of Symptoms by Adolescents and Young Adults With Type 1 Diabetes During Experimental Induction of Mild Hypoglycemia
Authors: Ryan Christopher M. , Dulay Daisy , Suprasongsin Chittiwat , Becker Dorothy J.
Published: March 2007

OBJECTIVE—To identify hormonal, psychological, and demographic predictors of symptom detection and accuracy of blood glucose estimation during mild hypoglycemia in adolescents and young adults with type 1 diabetes.

RESEARCH DESIGN AND METHODS—During an insulin-glucose clamp study, 53 adolescents and 19 young adults estimated blood glucose levels and reported symptoms at euglycemia and after 30 min of mild hypoglycemia (3.3 mmol/l). Epinephrine and pancreatic polypeptide were measured, and both change in anxiety level during hypoglycemia and baseline level of anxiety were measured with the Spielberger Anxiety Inventory. Elevated levels of anxiety during euglycemia were used as an indicator of the psychological trait “negative affectivity.” Previous studies have suggested that individuals with higher negative affectivity are more internally focused and, therefore, more likely to report somatic and visceral changes.

RESULTS—During mild hypoglycemia, 42% of the sample subjects reported an increase in autonomic symptoms; 29% reported an increase in neuroglycopenic symptoms, and 28% estimated blood glucose levels accurately (within 10% of actual). Hormonal excursions did not predict any outcome, but higher anxiety levels during the euglycemic baseline were associated with better detection of hypoglycemic symptoms and more accurate estimation of blood glucose values after controlling for change in anxiety level during hypoglycemia.

CONCLUSIONS—Psychological factors such as elevated anxiety levels (“negative affectivity”) can influence blood glucose estimation and symptom detection in adolescents and young adults and may explain why some individuals are more adept than others at reducing their risk of severe hypoglycemia after participation in a formal blood glucose awareness training program.
ACE Gene Insertion/Deletion Polymorphism Associated With 1998 World Health Organization Definition of Metabolic Syndrome in Chinese Type 2 Diabetic Patients
Authors: Lee Yau-Jiunn , Tsai Jack C.R.
Published: March 2007

OBJECTIVE—Because ACE insertion/deletion (I/D) polymorphism has been shown to be associated with diabetes, hypertension, coronary artery diseases, and diabetic nephropathy, and because plasma ACE concentration has been found to be associated with plasma triglyceride and total cholesterol levels in patients with type 2 diabetes, the goal of this study was to investigate whether ACE gene I/D polymorphism is associated with metabolic syndrome in Chinese subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 711 patients with type 2 diabetes and 750 control subjects were studied. The ACE I/D polymorphism was determined by PCR. The definition and criteria of metabolic syndrome used in this study matched those proposed in the 1998 World Health Organization classification.

RESULTS—Of 711 patients with type 2 diabetes, 534 (75.1%) fulfilled the criteria for metabolic syndrome. The prevalence of metabolic syndrome in control subjects with II, ID, and DD genotype was 9.4, 11.5, and 15.4%, respectively, and in patients with type 2 diabetes, it was 68.6, 79.2, and 86.1%, respectively. The ACE I/D polymorphism was significantly associated with the syndrome in patients with type 2 diabetes (P = 0.001). When pooling the control subjects with diabetic patients, the prevalence of metabolic syndrome in the whole study group with II, ID, and DD genotype was 37.9, 44.5, and 51.0%, respectively, and ACE I/D polymorphism was still significantly associated with metabolic syndrome (P = 0.003). Diabetic patients with DD genotype were also found to have a higher prevalence of dyslipidemia (II/ID/DD = 43.1/53.1/65.8%, P < 0.001) and albuminuria (36.0/44.6/50.6%, P = 0.018) and to have higher serum triglyceride levels (II, ID, and DD = 155 ± 114, 170 ± 140, and 199 ± 132 mg/dl, respectively, P < 0.05). Control subjects with DD genotype were also found to have a higher prevalence of albuminuria or more advanced nephropathy (II/ID/DD = 5.7/14.0/15.4%, P = 0.001), whereas the prevalence of dyslipidemia was not found to be statistically different in the control group. When pooling control with diabetic subjects, ACE genotype could still be significantly associated with dyslipidemia (II/ID/DD = 34.7/41.3/52.2%, P < 0.001) and albuminuria or more advanced nephropathy (20.3/28.9/33.1%, P < 0.001). Diabetic patients with metabolic syndrome were found to have higher serum uric acid levels than those without metabolic syndrome (6.4 ± 1.8 vs. 5.3 ± 1.4 mg/dl, P < 0.01).

CONCLUSIONS—The ACE I/D polymorphism was found to be associated with metabolic syndrome in Chinese patients with type 2 diabetes. This finding may provide genetic evidence to explain the clustering of metabolic syndrome and suggests that the renin-angiotensin system is involved in the pathophysiology of metabolic derangement in patients with type 2 diabetes.
The Forefoot-to-Rearfoot Plantar Pressure Ratio Is Increased in Severe Diabetic Neuropathy and Can Predict Foot Ulceration
Authors: Caselli Antonella , Pham Hau , Giurini John M. , Armstrong David G. , Veves Aristidis
Published: March 2007

OBJECTIVE—We have previously demonstrated that high plantar pressures can predict foot ulceration in diabetic patients. The aim of the present study was to evaluate both the relationship between forefoot and rearfoot plantar pressure in diabetic patients with different degrees of peripheral neuropathy and their role in ulcer development.

RESEARCH DESIGN AND METHODS—Diabetic patients of a 30-month prospective study were classified according to the neuropathy disability score: scores of 0, 1–5, 6–16, and 17–28 are defined as absent (n = 20), mild (n = 66), moderate (n = 95), and severe (n = 57) neuropathy, respectively. The F-Scan mat system was used to measure dynamic plantar pressures. The peak pressures under the forefoot and the rearfoot were selectively measured for each foot, and the forefoot-to-rearfoot ratio (F/R ratio) was calculated.

RESULTS—Foot ulcers developed in 73 (19%) feet. The peak pressures were increased in the forefoot of the severe and moderate neuropathic groups compared with the mild neuropathic and nonneuropathic groups (6.2 ± 4.5 and 3.8 ± 2.7 vs. 3.0 ± 2.1 and 3.3 ± 2.1 kg/cm2 [mean ± SD], respectively; P < 0.0001). The rearfoot pressures were also higher in the severe and moderate neuropathic groups compared with the mild neuropathic and nonneuropathic groups (3.2 ± 2.0 and 3.2 ± 1.9 vs. 2.5 ± 1.3 and 2.3 ± 1.0, respectively; P < 0.0001). The F/R ratio was increased only in the severe group compared with the moderate and mild neuropathic and nonneuropathic groups (2.3 ± 2.4 vs. 1.5 ± 1.2, 1.3 ± 0.9, and 1.6 ± 1.0, respectively; P < 0.0001). In a logistic regression analysis, both forefoot pressure (odds ratio 1.19 [95% CI 1.11–1.28], P < 0.0001) and the F/R ratio (1.37 [1.16–1.61], P < 0.0001) were related to risk of foot ulceration, whereas rearfoot pressure was not.

CONCLUSIONS—Both the rearfoot and forefoot pressures are increased in the diabetic neuropathic foot, whereas the F/R ratio is increased only in severe diabetic neuropathy, indicating an imbalance in pressure distribution with increasing degrees of neuropathy. This may lend further evidence toward the concept that equinus develops in the latest stages of peripheral neuropathy and may play an important role in the etiology of diabetic foot ulceration.
The American Diabetes Association and World Health Organization Classifications for Diabetes
Authors: Rodriguez Beatriz L. , Abbott Robert D. , Fujimoto Wilfred , Waitzfelder Beth , Chen Randi , Masaki Kamal , Schatz Irwin , Petrovitch Helen , Ross Webster , Yano Katsuhiko , Blanchette Patricia L. , Curb J. David
Published: March 2007

OBJECTIVE—To compare the prevalence of diabetes according to the American Diabetes Association (ADA) and World Health Organization (WHO) classifications in a sample of elderly Japanese-American men; to examine the association with total and cardiovascular mortality by diabetes status using both classifications; and to determine whether the fasting or 2-h glucose measurement is a stronger predictor of adverse outcomes.

RESEARCH DESIGN AND METHODS—Examinations given from 1991 to 1993 in the Honolulu Heart Program were used as baseline for these analyses. Subjects were 71–93 years of age at that time and were followed for total and cardiovascular disease mortality for up to 7 years.

RESULTS—A total of ∼66% of individuals who had diabetes by WHO criteria were missed when the ADA definition was used. The relative risks of total and cardiovascular mortality for those with versus those without diabetes were similar for both definitions; however, when fasting and postload glucose measures were analyzed as continuous variables, the 2-h measurement was a superior predictor and was independent of fasting glucose. In contrast, fasting glucose was not an independent predictor of these outcomes in the presence of the 2-h measurement.

CONCLUSIONS—The prevalence of glucose metabolism abnormalities was very high among elderly Japanese-American men. The WHO classification was superior to the ADA classification in identification of subjects at high risk for adverse outcomes. Therefore, we conclude that the 2-h glucose measurement is valuable and should be retained in epidemiologic studies.
Comparison of the Effects of Three Insulinotropic Drugs on Plasma Insulin Levels After a Standard Meal
Authors: Cozma Lawrence S. , Luzio Stephen D. , Dunseath Gareth J. , Langendorg Kirsten W. , Pieber Thomas , Owens David R.
Published: March 2007

OBJECTIVE—To compare the effects of repaglinide, glipizide, and glibenclamide on insulin secretion and postprandial glucose after a single standard 500-kcal test meal.

RESEARCH DESIGN AND METHODS—A total of 12 type 2 diabetic patients with early diabetes (mean HbA1c of 6.1%) and 12 matched control subjects were enrolled in this randomized, double-blind, crossover trial. Subjects received placebo, 2 mg repaglinide, 5 mg glipizide, and 5 mg glibenclamide in a random fashion during the trial. Administration of each drug was followed by a single standard 500-kcal test meal. A washout period of 7–12 days existed between the four study visits.

RESULTS—All three drugs were equally effective on the total prandial insulin secretion (area under the curve [AUC] −15 to 240 min). However, clear differences were noted in the early insulin secretion (AUC −15 to 30 min); both repaglinide and glipizide increased secretion in nondiabetic subjects by ∼61 and 34%, respectively, compared with placebo. In the diabetic patients, the difference versus placebo was 37 and 47%, respectively. The difference between glipizide and glibenclamide reached significance in both groups of subjects, whereas repaglinide was more effective than glibenclamide only in the healthy nondiabetic subject group. All three drugs were effective in decreasing total glucose AUC in the nondiabetic and diabetic population. In the nondiabetic subjects, however, repaglinide was significantly more effective than glibenclamide. The differences disappeared in the diabetic subjects, probably as a result of increased prevalence of insulin resistance in this group.

CONCLUSIONS—Repaglinide and glipizide but not glibenclamide significantly enhanced the early insulin secretion in both nondiabetic and diabetic subjects with preserved β-cell function after a single standard meal.
Animal Versus Plant Protein Meals in Individuals With Type 2 Diabetes and Microalbuminuria
Authors: Wheeler Madelyn L. , Fineberg S. Edwin , Fineberg Naomi S. , Gibson Reid G. , Hackward Laurie L.
Published: March 2007

OBJECTIVE—To determine, for individuals with type 2 diabetes and microalbuminuria, the effects of 6 weeks of meals containing plant-based protein (PP) versus meals with predominantly animal-based protein (AP) on renal function and secondarily on glycemia, lipid levels, and blood pressure.

RESEARCH DESIGN AND METHODS—In a randomized crossover trial, we compared 6 weeks of meals containing only PP with meals containing primarily AP (60% animal, 40% plant) in 17 subjects with type 2 diabetes and microalbuminuria treated with diet and/or oral antidiabetic agents. Protein content was equivalent to the average American diet, and calories provided weight maintenance. Nutrients were equivalent between the two diets. Meals were prepared and packaged by a metabolic kitchen staff and were sent home weekly. At the beginning and end of each 6-week period, subjects were studied for 36 h on a metabolic unit.

RESULTS—There were no significant differences between diets for glomerular filtration rate, renal plasma flow, albumin excretion rate, total cholesterol, HDL cholesterol, triglyceride area under the curve (AUC), glucose and insulin AUC, HbA1c, blood pressure, or serum amino acids. For both diets, at the end of the treatment periods as compared with baseline, total cholesterol was significantly lower (PP and AP: from 4.75 to 4.34 mmol/l, P < 0.01), HbA1c had significantly improved (PP: from 8.1 to 7.5%, P < 0.01; AP: from 7.9 to 7.4%, P < 0.01), and diastolic blood pressure was significantly lower (PP: from 83 to 80 mmHg, P < 0.02; AP: from 82 to 78, P < 0.02).

CONCLUSIONS—There is no clear advantage for the recommendation of diets containing only PP rather than diets containing protein that is primarily animal-based for individuals with type 2 diabetes and microalbuminuria. There are, however, potential lipid, glycemic, and blood pressure benefits for following a carefully constructed, weight-maintaining, healthy diet, regardless of protein source.
Tissue Factor Pathway Inhibitor and Other Endothelium-Dependent Hemostatic Factors in Elderly Individuals With Normal or Impaired Glucose Tolerance and Type 2 Diabetes
Authors: Leurs Paul B. , Stolk Ronald P. , Hamulyak Karly , van Oerle René , Grobbee Diederick E. , Wolffenbuttel Bruce H. R.
Published: March 2007

OBJECTIVE—Impaired glucose tolerance (IGT) is believed to be a prediabetic phase that precedes the development of type 2 diabetes. In elderly subjects, IGT and diabetes are both independently associated with the occurrence of cardiovascular disease. Endothelial damage precedes atherosclerotic changes of the vascular wall. Therefore, several markers of endothelial dysfunction were examined in elderly subjects with IGT and elderly patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1), and thrombomodulin were studied as markers of endothelial dysfunction in a population-based study of elderly subjects with normal glucose tolerance (NGT) or IGT and type 2 diabetes. In addition to these endothelium-dependent factors, we also investigated tissue factor pathway inhibitor (TFPI) activity in relation to metabolic parameters and cardiovascular risk factors.

RESULTS—All data were adjusted for age. Increased levels of vWF antigen, t-PA antigen, and PAI-1 activity were seen in the IGT and diabetic group compared with the NGT group. TFPI activity and thrombomodulin levels were increased in all elderly subjects, and no differences were seen between the groups. There was a positive association between HbA1c and TFPI activity and vWF antigen. Fasting blood glucose levels correlated with vWF antigen, t-PA antigen, and PAI-1 activity, whereas urine albumin excretion correlated with TFPI activity, vWF antigen, and PAI-1 activity. Serum insulin levels correlated strongly not only with vWF antigen and t-PA antigen but also with PAI-1 activity. This correlation did not change after further adjustment for serum glucose and HbA1c, which may suggest that in the elderly subjects, impaired fibrinolysis is probably associated with insulin resistance. There were no associations between the endothelium-dependent hemostatic factors and lipids, except for a negative correlation between HDL cholesterol and thrombomodulin.

CONCLUSIONS—In elderly subjects with IGT, several endothelium-dependent hemostatic factors are already consistently increased, indicating endothelial damage in this stage.
Acidic Drinking Water and Risk of Childhood-Onset Type 1 Diabetes
Authors: Stene Lars C. , Hongve Dag , Magnus Per , Rønningen Kjersti S. , Joner Geir
Published: March 2007

OBJECTIVE—To estimate the associations of acidity and concentration of selected minerals in household tap water with the risk of type 1 diabetes.

RESEARCH DESIGN AND METHODS—We designed a population-based case-control study with 64 cases of type 1 diabetes and 250 randomly selected control subjects. Acidity, color, and mineral content were measured in tap water from each participant’s household.

RESULTS—Tap water pH 6.2–6.9 was associated with a fourfold higher risk of type 1 diabetes compared with pH ≥7.7 (OR 3.73, 95% CI 1.52–9.15). This result was similar after exclusion of individuals with the highly protective HLA-DQB1*0602 allele, but adjustment for maternal education, urban/rural residence, sex, and age tended to strengthen the estimated association. Higher tap water concentration of zinc was associated with lower risk of type 1 diabetes after adjustment for pH and other possible confounders, but the overall association was strictly not significant.

CONCLUSIONS—These results suggest the possibility that quality of drinking water influences the risk of type 1 diabetes. The possible mechanisms by which water acidity or mineral content may be involved in the etiology of type 1 diabetes remain unknown, but the mechanisms are most likely indirect and may involve an influence on survival of microorganisms in the water.
Prevalence and Concomitants of Glucose Intolerance in European Obese Children and Adolescents
Authors: Invitti Cecilia , Guzzaloni Gabriele , Gilardini Luisa , Morabito Francesco , Viberti Giancarlo
Published: March 2007

OBJECTIVE—The worldwide increase in the prevalence of childhood obesity is reaching epidemic proportions and is associated with a dramatic rise in cases of type 2 diabetes. The prevalence of glucose intolerance and its determinants and the relation of cardiovascular risk factors with levels of glycemia and degree of obesity were studied in grossly obese children of European origin.

RESEARCH DESIGN AND METHODS—A total of 710 grossly obese Italian children (SD score [SDS] of BMI 3.8 ± 0.7) aged 6–18 years, including 345 male subjects, underwent an oral glucose tolerance test. Insulin resistance and insulin secretion were estimated using the homeostasis model assessment for insulin resistance and the insulinogenic index, respectively. Fibrinogen, C-reactive protein, lipids, and uric acid were measured. The 2-h postload glucose and degree of obesity, calculated as the SDS of weight/height2, were used as dependent variables.

RESULTS—The prevalence of glucose intolerance was 4.5%. Insulin resistance (P < 0.0001), impaired insulin secretion (P < 0.0001), and diastolic blood pressure (BP) (P < 0.05) were significantly and independently related to 2-h postload glucose values. The degree of obesity did not relate to insulin resistance but was independently correlated with inflammatory proteins, uric acid, and systolic BP, variables that were often abnormal in this population.

CONCLUSIONS—In these grossly obese children, both insulin resistance and impaired insulin secretion contribute to the elevation of glycemia, and the degree of obesity is related to cardiovascular risk factors independently of insulin resistance.
Discordance Between HbA1c and Fructosamine
Authors: Cohen Robert M. , Holmes Yancey R. , Chenier Thomas C. , Joiner Clinton H.
Published: March 2007

OBJECTIVE—Discordances between HbA1c and other measures of glycemic control are common in clinical practice and remain unexplained. We developed a measure of discordance between HbA1c and fructosamine (FA) (glycosylated serum proteins) to conduct a systematic evaluation. We termed this the glycosylation gap (GG) and sought to determine its relationship to diabetic nephropathy.

RESEARCH DESIGN AND METHODS—Measurements of HbA1c and FA on the same sample in 153 people were used to calculate GG, defined as the difference between measured HbA1c and HbA1c predicted from FA based on the population regression of HbA1c on FA.

RESULTS—GG had a broad distribution (range, −3.2% to 5.5%); 40% of samples had values indicating major differences in prediction of complications risk by the measured versus predicted HbA1c. GG was highly correlated (r = 0.81) between measurements repeated in 65 patients 23 ± 2 weeks apart, indicating that the discordances are reliable and not explained by differences in turnover of underlying proteins. In 40 patients with type 1 diabetes of ≥15 years’ duration, an increase in GG by 1% was associated with a 2.9-fold greater frequency of increasing nephropathy stage (P = 0.0014). GG was −0.8 ± 0.2% in subjects with no nephropathy, −0.3 ± 0.2% with microalbuminuria/hypertension, and 0.7 ± 0.3% in subjects with proteinuria or renal dysfunction (P < 0.05). GG correlated better with nephropathy than did either HbA1c or FA alone in this population.

CONCLUSIONS—The glycosylation gap may be a useful clinical research tool for evaluating physiologic sources of variation in diabetic complications beyond glycemic control.
Effects of Injectable or Implantable Progestin-Only Contraceptives on Insulin-Glucose Metabolism and Diabetes Risk
Authors: Kahn Henry S. , Curtis Kathryn M. , Marchbanks Polly A.
Published: March 2007

Progestin-only contraceptives administered by injection (Depo-Provera) or subcutaneous implant (Norplant) have been available to U.S. women for about a decade. Two epidemiological studies found their use associated with increased incidence of type 2 diabetes. In reviewing publications relating progestin injections and implants to glucose metabolism, 25 studies of various study designs and laboratory methods were identified that reported at least one insulin value in nondiabetic women. Research subjects were usually nonobese and often from developing countries. Of eight studies that performed sequential oral glucose tolerance tests (OGTTs) after at least 6 months of Depo-Provera or Norplant use, seven found significant elevations (approximate doubling) of insulin at 2 or 3 h after glucose challenge; the effects on fasting, half-hour, or 1-h postchallenge insulin values were less consistent. The three studies that performed sequential intravenous glucose tolerance tests (IVGTTs) on injection users all found an increased early-phase insulin response. One study used sequential hyperglycemic-hyperinsulinemic clamps to demonstrate reduced total-body glucose uptake per unit of insulin after 8 weeks of Norplant use. The metabolic studies generally did not show a reduction in the glucose tolerance of their nondiabetic subjects. However, compared with the lean and low-risk women who were usually selected for metabolic research, many U.S. women receiving these injections or implants may start out with increased insulin resistance due to greater weight, sedentary lifestyle, and family or childbearing histories. Additional research could help clarify whether exposure to injectable or implantable contraceptives leads to increased risk of type 2 diabetes and gestational diabetes in women with predisposing factors.
Sonographic Evaluation of Fetal Growth and Body Composition in Women With Different Degrees of Normal Glucose Metabolism
Authors: Parretti Elena , Carignani Lucia , Cioni Riccardo , Bartoli Elisa , Borri Patrizia , La Torre Pasquale , Mecacci Federico , Martini Elisabetta , Scarselli Gianfranco , Mello Giorgio
Published: March 2007

OBJECTIVE—To investigate the maternal demographic and metabolic factors contributing to the growth of fetal lean and fat body mass in women whose degree of glucose intolerance is less than that defining gestational diabetes in comparison with women with normal glucose metabolism.

RESEARCH DESIGN AND METHODS—Longitudinal sonographic examinations of 66 singleton fetuses without anomalies of nonobese mothers with abnormal oral glucose challenge test (GCT) results and without gestational diabetes (group 1) were compared with those of 123 singleton fetuses without anomalies of nonobese mothers with normal GCT values (group 2). Lean body mass measurements included head circumference, femur length, mid-upper arm, and mid-thigh central areas. Fat body mass measurements included the anterior abdominal wall thickness, the subscapular thickness, and the mid-upper arm and mid-thigh subcutaneous areas. All the women performed a 24-h glucose profile on the day preceding the ultrasound scan. Multivariate logistic regression analysis established best-fit equations for fetal sonographic measurements of fat and lean body mass. Independent variables included groups 1 and 2, maternal age, parity, prepregnancy BMI, gestational age, weight gain during pregnancy, fetal sex, and the following averaged 24-h profile maternal capillary blood glucose values: preprandial, 1-h postprandial, and 2-h postprandial.

RESULTS—No difference was found between the two groups with respect to fetal lean body mass parameters; the factors that contributed significantly and most frequently were gestational age and fetal sex (male). With respect to fetal fat body mass, all the measurements were significantly higher in group 1 than in group 2. In all instances, the significantly contributing factors were gestational age and maternal 1-h postprandial glucose values, whereas another frequent contributor was prepregnancy BMI.

CONCLUSIONS—Our study suggests the possibility of using sonographically determined fetal fat and lean mass measurements as indicators of body composition. The assessment of these parameters, achievable in a noninvasive and reproducible fashion in pregnancies complicated by glucose intolerance, might enable the real-time detection of fetal overgrowth and disproportion, thus opening the possibility of exploring interventions to limit fetal fat accretion, birth weight, and potential resulting morbidity.
French Multicentric Survey of Outcome of Pregnancy in Women With Pregestational Diabetes
Authors:   Diabetes and Pregnancy Group, France
Published: March 2007

OBJECTIVE—To evaluate perinatal outcome in pregnancies in women with type 1 and type 2 diabetes and the influence of preconception care 10 years after the St. Vincent’s declaration.

RESEARCH DESIGN AND METHODS—A cross-sectional study was conducted in 12 perinatal centers in France in 2000-2001. The main investigated outcomes were perinatal mortality, major congenital malformations, and preterm delivery.

RESULTS—Among 435 single pregnancies, 289 (66.4%) were from women with type 1 and 146 (33.6%) from women with type 2 diabetes. Perinatal mortality rate was 4.4% (0.7% national rate), severe congenital malformations rate was 4.1% (2.2% national rate), and preterm delivery rate was 38.2% (4.7% national rate). Preconception care was provided in 48.5% women with type 1 diabetes and in 24.0% women with type 2 diabetes. Women whose first trimester HbA1c was >8% had higher rates of perinatal mortality (9.2 vs. 2.5%; odds ratio 3.9; 95% CI 1.5–9.7; P < 0.005), major congenital malformations (8.3 vs. 2.5%; 3.5; 1.3–8.9; P < 0.01), and preterm delivery (57.6 vs. 24.8%; 1.4; 1.1–1.7; P < 0.005) than those with first trimester HbA1c <8%. These results are similar to those reported in France in 1986–1988.

CONCLUSIONS—Pregnancies in women with diabetes are still poorly planned and complicated by higher rates of perinatal mortality and major congenital malformations. Despite knowledge of the importance of intensified glycemic control before pregnancy, reaching the St. Vincent’s target needs further implementation in France.
Identifying Hepatic Nuclear Factor 1α Mutations in Children and Young Adults With a Clinical Diagnosis of Type 1 Diabetes
Authors: Lambert A. Paul , Ellard Sian , Allen Lisa I.S. , Gallen Ian W. , Gillespie Kathleen M. , Bingley Polly J. , Hattersley Andrew T.
Published: March 2007

OBJECTIVE—HNF-1α gene mutations (MODY3) present with marked hyperglycemia in lean young adults and may, therefore, be mistaken for type 1 diabetes, with implications for individual treatment and risk of diabetes in other family members. We examined the prevalence of HNF-1α mutations in families with three generations of diabetes identified in a population-based study of childhood diabetes, representing a subpopulation in which misclassification was likely.

RESEARCH DESIGN AND METHODS—In a study population of 1,470 families, 36 families (2.4%) with three affected generations were identified. In the 18 families in whom DNA samples were available, islet autoantibody testing, HLA class II genotyping, and HNF-1α sequencing were performed.

RESULTS—At least one islet autoantibody was found in 13 of 14 probands, and diabetes-associated HLA class II haplotypes were found in 17 of 18. One proband, who had no islet autoantibodies and was homozygous for the protective HLA haplotype DRB1*02-DQB1*0602, had a novel HNF-1α heterozygous nonsense mutation (R54X). This mutation cosegregated with diabetes in the family. The proband, his brother, mother, and maternal grandmother were diagnosed with type 1 diabetes aged 14–18 years and treated with insulin (0.39–0.74 units/kg) from diagnosis. The mother has since been successfully transferred to sulfonylurea treatment.

CONCLUSIONS—Family history alone is of limited value in identification of individuals with HNF-1α mutations, and we propose a stepwise approach that restricts sequencing of the HNF-1α gene to those with a family history of diabetes who also test negative for islet autoantibodies.
Delineation of Prevalence and Risk Factors for Early Coronary Artery Disease by Electron Beam Computed Tomography in Young Adults With Type 1 Diabetes
Authors: Starkman Harold S. , Cable Gregory , Hala Virginia , Hecht Harvey , Donnelly Christine M.
Published: March 2007

OBJECTIVE—Type 1 diabetes increases the risk for coronary artery disease (CAD), but limited information is available regarding the early natural history of this process. Electron beam tomography (EBT) can measure coronary artery calcification (CAC), an early marker for CAD. This study was designed to assess the prevalence and risk factors for CAC in young adults with established type 1 diabetes.

RESEARCH DESIGN AND METHODS—A total of 101 subjects aged 17–28 years with type 1 diabetes of over 5 years’ duration and no history of heart disease underwent cardiac EBT with calcium scoring. Medical histories were obtained and physical examinations were conducted to document the presence of cardiac risk factors as well as evidence of microvasculopathy and diabetic arthropathy. Laboratory evaluation included measurement of fasting lipoproteins, homocysteine concentration, lipoprotein(a) [Lp(a)], urinary microalbumin, and HbA1c. Contingency table analysis was used to assess bivariate relationships. Logistic regression was employed to construct a parsimonious model of independent risk factors.

RESULTS—Eleven subjects (10.9%) had CAC. Smokers were nearly five times more likely than nonsmokers to have CAC (P = 0.03). In addition, each 0.36-mm/l increment of Lp(a) was associated with a 10% increased risk for CAC (P = 0.05) after controlling for potentially confounding factors. There was no association of other CAD or diabetes risk factors studied with CAC.

CONCLUSIONS—The prevalence of early CAD as evidenced by CAC in young adults with type 1 diabetes is significant. Smoking and Lp(a) levels independently predict the presence of CAC. Additional study is necessary to delineate the natural history of CAC and the role of risk factor modification to prevent progression of CAD in this high-risk population.