bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin action and insulinemia are closely related to the fasting complement C3, but not acylation stimulating protein concentration.
Authors: Weyer C , Tataranni P A , Pratley R E
Published: March 2007

OBJECTIVE: An elevated C3 concentration has been reported in people with obesity, type 2 diabetes, hypertension, and dyslipidemia, and has been proposed to play a role in the development of atherosclerosis. We hypothesized that an elevated C3 concentration might be linked to insulin resistance and/or hyperinsulinemia, abnormalities commonly observed in association with the above conditions. RESEARCH DESIGN AND METHODS: Fasting concentrations of C3 and acylation stimulating protein (ASP, C3adesarg), a cleavage product of C3 recently found to stimulate glucose uptake in vitro, were measured in 33 healthy nondiabetic Pima Indians (14 women and 19 men; age 27 +/- 1 and body fat 33 +/- 1%, means +/- SEM). Subjects were characterized for body composition dual-energy X-ray absorptiometry, insulin action (insulin-stimulated glucose disposal [M], hyperinsulinemic glucose clamp), and glucose tolerance (75-g oral glucose tolerance test). RESULTS: Fasting C3 and ASP concentrations were positively correlated (r = 0.43, P < 0.05). Fasting C3 concentration was closely related to percent body fat (r = 0.77), M (r = -0.75), and fasting insulin concentration (r = 0.72) (all P < 0.0001). Fasting C3 concentrations remained significantly related to M and fasting insulin after adjusting for percent body fat (partial r = -0.53 and 0.33, both P < 0.05). In subjects with impaired glucose tolerance, fasting C3 concentrations were higher than in those with normal glucose tolerance--a difference that remained after adjustment for percent body fat and M. We found that fasting ASP concentrations were significantly related to percent body fat (r = 0.37, P < 0.05), but not to M or fasting insulin. CONCLUSIONS: In Pima Indians, fasting C3 concentration is closely related to adiposity, insulin action, and fasting insulin levels and may thus be a mediator for the postulated link between obesity, insulin resistance, hyperinsulinemia, and possibly atherosclerosis.
Association of HELLP syndrome with autoimmune antibodies and glucose intolerance.
Authors: Weitgasser R , Spitzer D , Kartnig I , Zajc M , Staudach A , Sandhofer F
Published: March 2007

OBJECTIVE: HELLP syndrome is a severe form of preeclampsia, characterized by hemolysis (H), elevated liver enzymes (EL), and low platelets (LP), whose pathogenesis is unclear. Autoimmunity is thought to play an important role. After the observation of development of type 1 diabetes in a patient with HELLP syndrome, we assumed a possible disease association based on autoimmune reactions. RESEARCH DESIGN AND METHODS: We examined 70 women with HELLP syndrome for the presence of autoimmune markers and glucose intolerance. Free thyroxine, triiodothyronine, thyroid-stimulating hormone, anti-thyroglobulin antibodies, thyroperoxidase antibodies, thyrotropin receptor antibodies, antinuclear antibodies (ANAs) and anti-DNA, islet cell antibodies, GADA, an oral glucose tolerance test, and HbA1c were determined postpartum. Patients with positive autoimmune markers or glucose intolerance were prospectively followed and repeated testing was performed. There were 60 women with a normal course of pregnancy matched for age, BMI, and number of pregnancies, which served as a control group. RESULTS: From the HELLP patients, 22 (31%) compared with only 6 (10%) control subjects had autoimmune antibodies (P < 0.01). There were 16 HELLP patients (23%) who exhibited only 1 kind of autoantibody (5 ANA, 9 thyroid antibodies, and 2 GADA), whereas in 6 HELLP patients (8.5%) 2 different antibodies were found. In all but 4 patients of the study group, these antibodies disappeared during 3 +/- 1.5 years of follow-up. Glucose intolerance was detected in 22 (31%) of the HELLP patients, 17 of them had impaired glucose tolerance (IGT), and 5 had diabetes, whereas only 4 subjects (6.5%) with IGT at postpartum were found in the control group (P < 0.01). During the follow-up, 2 HELLP patients were still diabetic and another 2 HELLP patients (1 GADA positive) had IGT versus 1 control subject. CONCLUSIONS: Our data give evidence that HELLP syndrome is associated with various autoimmune antibodies and glucose intolerance. Because glucose intolerance and/or autoimmune markers persisted during long-term follow-up in 6 patients with HELLP syndrome versus 1 in the control group, it may become advisable to reexamine patients with HELLP syndrome for detection of diabetes and autoimmune disorders.
MspI polymorphism at +83 bp in intron 1 of the human apolipoprotein A1 gene is associated with elevated levels of HDL cholesterol and apolipoprotein A1 in nondiabetic subjects but not in type 2 diabetic patients with coronary heart disease.
Authors: Pulkkinen A , Viitanen L , Kareinen A , Lehto S , Laakso M
Published: March 2007

OBJECTIVE: Elevated HDL cholesterol and its principal carrier protein apolipoprotein a1 [apo(a1)] are associated with reduced risk of coronary heart disease (CHD). No studies are available on the impact of the -75-bp and/or +83-bp polymorphisms of the apo(a1) gene on HDL cholesterol and apo(a1) levels in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We determined the prevalence of the: -75-bp and +83-bp polymorphisms of the apo(a1) gene by restriction fragment length polymorphism analysis among 308 unrelated nondiabetic subjects with CHD and among 251 unrelated patients with type 2 diabetes with CHD and in randomly selected 82 healthy men (CHD-). RESULTS: The rare M1- and M2- allele frequencies of the apo(a1) gene were 23 and 1.8%, respectively, among control subjects; 20 and 1.5%, respectively, among nondiabetic subjects with CHD; and 22 and 2.6%, respectively, among patients with type 2 diabetes and CHD (NS). Nonsmoking nondiabetic subjects with CHD having the M2+- genotype had higher HDL cholesterol (1.48 +/- 0.19 vs. 1.23 +/- 0.02 mmol/l, P < 0.01) and apo(a1) (1.43 +/- 0.10 vs. 1.36 +/- 0.02 g/l, P < 0.05) levels than subjects with the M2++ genotype, even after adjustment for confounding factors. This association was not found among patients with type 2 diabetes and CHD. CONCLUSIONS: We conclude that the +83-bp polymorphism of the apo(a1) gene is associated with elevated HDL cholesterol and apo(a1) levels in Finnish nondiabetic subjects but not in patients with type 2 diabetes.
Long-term follow-up in diabetic Charcot feet with spontaneous onset.
Authors: Fabrin J , Larsen K , Holstein P E
Published: March 2007

OBJECTIVE: To assess the long-term results after Charcot breakdown with spontaneous onset in diabetic feet. RESEARCH DESIGN AND METHODS: This study was retrospective. A total of 115 patients (140 feet), 107 with acute deformity and 8 with chronic Charcot deformity, were followed for a median of 48 months (range 6-114). The routine treatment for acute cases was a weight-off regimen with crutches and foot protection with therapeutic shoes until skin temperature had normalized followed by increased weightbearing and the use of bespoke shoes or modification of conventional shoes. RESULTS: The incidence of Charcot deformity was 0.3%/year in the diabetic population investigated. About half of the patients were active in their jobs. Major complications were encountered in 5 (4%) of the patients that required surgical intervention: arthrodesis for unstable malaligned ankles in 3 subjects (1 bilaterally) and major amputation in 2 subjects for unstable ankle and pressure sores. Minor complications were recorded in 43% of subjects: new attacks of Charcot breakdown in 41 patients (36%) and/or foot ulceration in 43 patients (37%) that required minor surgical procedures for 11 patients. All healed except in 2 patients: 1 patient died before the Charcot fractures had healed, and 1 patient died with an unhealed ulcer. No patient lost the ability to walk independently. CONCLUSIONS: Major surgical procedures in only 4% were particularly related to patients with Charcot deformities in the ankle. Minor complications were recorded in about half of the patients. Lifelong foot care is required for diabetic patients with Charcot feet.
Depression and poor glycemic control: a meta-analytic review of the literature.
Authors: Lustman P J , Anderson R J , Freedland K E , de Groot M , Carney R M , Clouse R E
Published: March 2007

OBJECTIVE: Depression is common among patients with diabetes, but its relationship to glycemic control has not been systematically reviewed. Our objective was to determine whether depression is associated with poor glycemic control. RESEARCH DESIGN AND METHODS: Medline and PsycINFO databases and published reference lists were used to identify studies that measured the association of depression with glycemic control. Meta-analytic procedures were used to convert the findings to a common metric, calculate effect sizes (ESs), and statistically analyze the collective data. RESULTS: A total of 24 studies satisfied the inclusion and exclusion criteria for the meta-analysis. Depression was significantly associated with hyperglycemia (Z = 5.4, P < 0.0001). The standardized ES was in the small-to-moderate range (0.17) and was consistent, as the 95% CI was narrow (0.13-0.21). The ES was similar in studies of either type 1 or type 2 diabetes (ES 0.19 vs. 0.16) and larger when standardized interviews and diagnostic criteria rather than self-report questionnaires were used to assess depression (ES 0.28 vs. 0.15). CONCLUSIONS: Depression is associated with hyperglycemia in patients with type 1 or type 2 diabetes. Additional studies are needed to establish the directional nature of this relationship and to determine the effects of depression treatment on glycemic control and the long-term course of diabetes.
The 1997 American Diabetes Association and 1999 World Health Organization criteria for hyperglycemia in the diagnosis and prediction of diabetes.
Authors: Gabir M M , Hanson R L , Dabelea D , Imperatore G , Roumain J , Bennett P H , Knowler W C
Published: March 2007

OBJECTIVE: The 1997 American Diabetes Association (ADA) and the 1985 and 1999 World Health Organization (WHO) criteria for diabetes and hyperglycemia differ. The appropriateness of these diagnostic criteria in terms of individuals identified as abnormal and their prognosis has been debated. The purpose of this study is to compare the classifications of people by these criteria and to compare fasting and postload plasma glucose concentrations in the prediction of diabetes. RESEARCH DESIGN AND METHODS: The frequencies of diabetes by the 3 sets of criteria were compared in 5,023 adult Pima Indians not taking hypoglycemic drugs. Among nondiabetic subjects, fasting plasma glucose (FPG) and 2-h postload plasma glucose (2-h PG) concentrations and categories of impaired glucose regulation or diabetes were evaluated as predictors of diabetes defined by 1999 WHO criteria. RESULTS: The frequency of diabetes was 12.5% by 1997 ADA criteria, 14.6% by 1985 WHO criteria, and 15.3% by 1999 WHO criteria. The incidence of diabetes was strongly related to higher FPG and 2-h PG, each of which had very similar predictive powers. Impaired glucose tolerance (IGT) was more common than impaired fasting glucose (IFG) (15 vs. 5%), but the 5-year incidence of diabetes was higher in IFG than IGT (37 vs. 24%). CONCLUSIONS: The prevalence and incidence of diabetes are somewhat lower with the ADA criteria than with the 1985 or 1999 WHO criteria. The intermediate categories of glycemia differ substantially IFG defines a smaller number of people who are at higher risk of developing diabetes than those with IGT. More people at high risk of diabetes could be identified by using either IFG or IGT, as recommended by the 1999 WHO criteria, or by using the FPG concentration alone, but with a lower cutoff value.
Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group.
Authors: Yki-Järvinen H , Dressler A , Ziemen M ,   HOE 901/300s Study Group
Published: March 2007

OBJECTIVE: Available basal insulin formulations do not provide a constant and reliable 24-h insulin supply. We compared the efficacy and safety of glargine (a long-acting insulin analog) and NPH insulins in insulin-naive type 2 diabetic patients treated with oral antidiabetic agents. RESEARCH DESIGN AND METHODS: There were 426 type 2 diabetic patients (age 59 +/- 9 years, BMI 28.9 +/- 4.3 kg/m2, mean +/- SD) with poor glycemic control on oral antidiabetic agents randomized to treatment for 1 year with bedtime insulin glargine or bedtime NPH insulin. Oral agents were continued unchanged. The fasting blood glucose (FBG) target was 6.7 mmol/l (120 mg/dl). RESULTS: Average glycemic control improved similarly with both insulins (HbA(1c), [reference range <6.5%] 8.3 +/- 0.1 vs. 8.2 +/- 0.1% at 1 year, glargine vs. NPH, mean +/- SEM, P < 0.001 vs. baseline for both). However, there was less nocturnal hypoglycemia (9.9 vs. 24.0% of all patients, glargine vs. NPH, P < 0.001) and lower post-dinner glucose concentrations (9.9 +/- 0.2 vs. 10.7 +/- 0.3 mmol/l, P < 0.02) with insulin glargine than with NPH. Insulin doses and weight gain were comparable. In patients reaching target FBG, HbA(1c) averaged 7.7 and 7.6% in the glargine and NPH groups at 1 year. CONCLUSIONS: Use of insulin glargine compared with NPH is associated with less nocturnal hypoglycemia and lower post-dinner glucose levels. These data are consistent with peakless and longer duration of action of insulin glargine compared with NPH. Achievement of acceptable average glucose control requires titration of the insulin dose to an FBG target < or =6.7 mmol/l. These data support use of insulin glargine instead of NPH in insulin combination regimens in type 2 diabetes.
Bromocriptine: a novel approach to the treatment of type 2 diabetes.
Authors: Pijl H , Ohashi S , Matsuda M , Miyazaki Y , Mahankali A , Kumar V , Pipek R , Iozzo P , Lancaster J L , Cincotta A H , DeFronzo R A
Published: March 2007

OBJECTIVE: In vertebrates, body fat stores and insulin action are controlled by the temporal interaction of circadian neuroendocrine oscillations. Bromocriptine modulates neurotransmitter action in the brain and has been shown to improve glucose tolerance and insulin resistance in animal models of obesity and diabetes. We studied the effect of a quick-release bromocriptine formulation on glucose homeostasis and insulin sensitivity in obese type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: There were 22 obese subjects with type 2 diabetes randomized to receive a quick-release formulation of bromocriptine (n = 15) or placebo (n = 7) in a 16-week double-blind study. Subjects were prescribed a weight-maintaining diet to exclude any effect of changes in body weight on the primary outcome measurements. Fasting plasma glucose concentration and HbA(1c) were measured at 2- to 4-week intervals during treatment. Body composition (underwater weighing), body fat distribution (magnetic resonance imaging), oral glucose tolerance (oral glucose tolerance test [OGTT]), insulin-mediated glucose disposal, and endogenous glucose production (2-step euglycemic insulin clamp, 40 and 160 mU x min(-1) x m(-2)) were measured before and after treatment. RESULTS: No changes in body weight or body composition occurred during the study in either placebo- or bromocriptine-treated subjects. Bromocriptine significantly reduced HbA(1c) (from 8.7 to 8.1%, P = 0.009) and fasting plasma glucose (from 190 to 172 mg/dl, P = 0.02) levels, whereas these variables increased during placebo treatment (from 8.5 to 9.1%, NS, and from 187 to 223 mg/dl, P = 0.02, respectively). The differences in HbA(1c) (delta = 1.2%, P = 0.01) and fasting glucose (delta = 54 mg/dl, P < 0.001) levels between the bromocriptine and placebo group at 16 weeks were highly significant. The mean plasma glucose concentration during OGTT was significantly reduced by bromocriptine (from 294 to 272 mg/dl, P = 0.005), whereas it increased in the placebo group. No change in glucose disposal occurred during the first step of the insulin clamp in either the bromocriptine- or placebo-treated group. During the second insulin clamp step, bromocriptine improved total glucose disposal from 6.8 to 8.4 mg x min(-1) kg(-1) fat-free mass (FFM) (P = 0.01) and nonoxidative glucose disposal from 3.3 to 4.3 mg min(-1) x kg(-1) FFM (P < 0.05), whereas both of these variables deteriorated significantly (P < or = 0.02) in the placebo group. CONCLUSIONS: Bromocriptine improves glycemic control and glucose tolerance in obese type 2 diabetic patients. Both reductions in fasting and postprandial plasma glucose levels appear to contribute to the improvement in glucose tolerance. The bromocriptine-induced improvement in glycemic control is associated with enhanced maximally stimulated insulin-mediated glucose disposal.
Comparison of continuous subcutaneous insulin infusion and multiple daily injection regimens using insulin lispro in type 1 diabetic patients on intensified treatment: a randomized study. The Study Group for the Development of Pump Therapy in Diabetes.
Authors: Hanaire-Broutin H , Melki V , Bessières-Lacombe S , Tauber J P
Published: March 2007

OBJECTIVE: To compare the efficacy of 2 intensified insulin regimens, continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI), by using the short-acting insulin analog lispro in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 41 C-peptide-negative type 1 diabetic patients (age 43.5+/-10.3 years; 21 men and 20 women, BMI 24.0+/-2.4 kg/m2, diabetes duration 20.0+/-11.3 years) on intensified insulin therapy (MDI with regular insulin or lispro, n = 9, CSII with regular insulin, n = 32) were included in an open-label randomized crossover study comparing two 4-month periods of intensified insulin therapy with lispro: one period by MDI and the other by CSII. Blood glucose (BG) was monitored before and after each of the 3 meals each day. RESULTS: The basal insulin regimen had to be optimized in 75% of the patients during the MDI period (mean number of NPH injections per day = 2.65). HbA1c values were lower when lispro was used in CSII than in MDI (7.89+/-0.77 vs. 8.24+/-0.77%, P<0.001). BG levels were lower with CSII (165+/-27 vs. 175+/-33 mg/dl, P<0.05). The SD of all the BG values (73+/-15 vs. 82+/-18 mg/dl, P<0.01) was lower with CSII. The frequency of hypoglycemic events, defined as BG levels <60 mg/dl, did not differ significantly between the 2 modalities (CSII 3.9+/-4.2 per 14 days vs. MDI 4.3+/-3.9 per 14 days). Mean insulin doses were significantly lower with CSII than with MDI (38.5+/-9.8 vs. 47.3+/-14.9 U/day. respectively, P< 0.0001). CONCLUSIONS: When used with external pumps versus MDI, lispro provides better glycemic control and stability with much lower doses of insulin and does not increase the frequency of hypoglycemic episodes.
Prevalence and risk factors of peripheral vascular disease in a selected South Indian population: the Chennai Urban Population Study.
Authors: Premalatha G , Shanthirani S , Deepa R , Markovitz J , Mohan V
Published: March 2007

OBJECTIVE: The epidemiology of peripheral vascular disease has rarely been studied in non-European populations. The purpose of this study was to determine the prevalence and risk factors of peripheral vascular disease (PVD) among South Indians. RESEARCH DESIGN AND METHODS: The Chennai Urban Population Study is an epidemiological study involving 2 residential areas in Chennai in South India. Of the 1,399 eligible subjects (> or =20 years of age), 1,262 (90.2%) participated in the study. All of the study subjects underwent an oral glucose tolerance test and were categorized as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or diabetes. Peripheral Doppler studies were performed on 50% of the study subjects, and PVD was defined as an ankle-brachial index (ABI) <0.9. RESULTS: The prevalence rates of PVD were 2.7, 2.9, and 6.3% in individuals with NGT, IGT, and diabetes, respectively The overall prevalence rate was 3.2%. Known diabetic subjects had a higher prevalence of PVD (7.8%) compared with newly diagnosed diabetic subjects (3.5%). PVD was uncommon until middle-age and then the prevalence rate increased dramatically. Univariate regression analysis showed age >50 years (odds ratio [OR] 6.3, 95% CI 2.1-20.6, P<0.001) and hypertension (OR 2.7, 0.9-7.3, P = 0.08) to be associated with PVD, whereas smoking and serum lipid levels showed no association. Multivariate regression analysis identified age as the most significant risk factor for PVD. Of the 90 subjects who had coronary artery disease (CAD), only 6 had PVD, and the positive predictive value of the ABI for CAD was only 30%. CONCLUSIONS: The prevalence of PVD in this urban South Indian population is considerably lower than that reported in European and U.S. studies and is in marked contrast to the high prevalence rate of CAD reported in this population.
Validation of a structured interview for the assessment of diabetes self-management.
Authors: Harris M A , Wysocki T , Sadler M , Wilkinson K , Harvey L M , Buckloh L M , Mauras N , White N H
Published: March 2007

OBJECTIVE: The authors developed and validated a semi-structured interview; the Diabetes Self-Management Profile (DSMP), to measure self-management of type 1 diabetes. The DSMP includes the following regimen components: exercise, management of hypoglycemia, diet, blood glucose testing, and insulin administration and dose adjustment. RESEARCH DESIGN AND METHODS: Families of youths with type 1 diabetes (n = 105) who were entering a controlled trial of intensive therapy (IT) versus usual care (UC) were administered the DSMP Analyses assessed the reliability and validity of the DSMP, including its associations with HbA1c and quality of life. RESULTS: The DSMP total score has adequate internal consistency (Cronbach's alpha 0.76), 3-month test-retest reliability (Pearson correlation, r = 0.67), inter-interviewer agreement (r = 0.94), and parent-adolescent agreement (r = 0.61). DSMP total scores (r = -0.28) and 3 subscales correlated significantly with HbA1c (diet [r = -0.27], blood glucose testing [r = -0.37], and insulin administration and dose adjustment [r = -0.25 ]). Adolescents' reports of self-management did not differ from parental reports. Higher DSMP scores were associated with more favorable quality of life for mothers and youths. CONCLUSIONS: The DSMP is a convenient measure that yields a reliable and valid assessment of diabetes self-management. Compared with extant similar measures, the DSMP is more strongly correlated with HbA1c.
Insulin sensitivity differs among ethnic groups with a compensatory response in beta-cell function.
Authors: Chiu K C , Cohan P , Lee N P , Chuang L M
Published: March 2007

OBJECTIVE: A drastic difference is evident in the prevalence of type 2 diabetes among ethnic groups. We examined the role of beta-cell function and insulin sensitivity in this disparity among 4 ethnic groups. RESEARCH DESIGN AND METHODS: beta-Cell function and insulin sensitivity were assessed in 77 healthy glucose-tolerant subjects using a hyperglycemic clamp (18 Asian-Americans, 9 African-Americans, 34 Caucasians, and 16 Mexican-Americans). RESULTS: A wide range of variation was evident in clinical features of the studied subjects. Insulin sensitivity index and the second-phase insulin response differed among the 4 groups (P = 0.0023 and P = 0.0082, respectively), whereas the first-phase insulin response was marginally different (P = 0.1090). Stepwise regression analysis revealed that ethnicity was an independent determinant for the insulin sensitivity index (P = 0.0014) after adjusting for sex, age, diastolic blood pressure, waist-to-hip ratio, and BMI. Also, a compensatory response of beta-cell function was observed among the ethnic groups. CONCLUSIONS: In this study, we observed a drastic difference in insulin sensitivity among the different ethnic groups and observed that their beta-cell function compensates for the prevailing insulin sensitivity. The difference in the prevalence of abnormal glucose tolerance in different ethnic groups could be a result of differences in insulin sensitivity
Familial clustering of arterial blood pressure, HDL cholesterol, and pro-insulin but not of insulin resistance and microalbuminuria in siblings of patients with type 2 diabetes.
Authors: Pontiroli A E , Monti L D , Pizzini A , Piatti P
Published: March 2007

OBJECTIVE: To test the hypothesis that selected abnormalities cluster in type 2 diabetic families. Offspring of patients with type 2 diabetes have a 40-60% chance of developing type 2 diabetes and an increased frequency of impaired glucose tolerance (IGT) or unknown diabetes. These offspring also show metabolic abnormalities of type 2 diabetes, such as insulin resistance, high insulin and pro-insulin, low HDL cholesterol levels, arterial hypertension, and microalbuminuria. RESEARCH DESIGN AND METHODS: We studied 87 families including at least one type 2 diabetic patient, i.e., 87 probands and 146 siblings; 60 spouses of probands with no family history of diabetes were compared with siblings. Familial clustering was evaluated by 2 methods: concordance of siblings and probands for a given abnormality (method 1) and intraclass correlation coefficients of values within each family (method 2). RESULTS: At oral glucose tolerance testing, 24 siblings had type 2 diabetes, 31 siblings had IGT, and 14 spouses had IGT (P = 0.0012 vs. siblings). With method 1, familial clustering occurred for microalbuminuria, insulin resistance, arterial hypertension, HDL cholesterol and pro-insulin levels; with method 2, familial clustering was observed for the same variables except for microalbuminuria. With both method 1 and 2, familial clustering for insulin resistance disappeared, whereas familial clustering for arterial blood pressure, HDL cholesterol, and pro-insulin remained after correction for BMI; after further restriction of analysis to probands and to siblings with normal glucose tolerance, familial clustering for pro-insulin was observed only with method 2. CONCLUSIONS: These data indicate that siblings of diabetic patients are at high risk for selected features of type 2 diabetes.
Hypoxic induction of vascular endothelial growth factor is markedly decreased in diabetic individuals who do not develop retinopathy.
Authors: Marsh S , Nakhoul F M , Skorecki K , Rubin A , Miller B P , Leibu R , Levy N S , Levy A P
Published: March 2007

OBJECTIVE: A small percentage of patients do not develop any evidence of diabetic retinopathy (DR) even after many years of diabetes. Vascular endothelial growth factor (VEGF) has been implicated in the development of DR. Therefore, we sought to determine if the regulation of VEGF differs in those patients who develop DR after many years of diabetes compared with those who do not develop DR. RESEARCH DESIGN AND METHODS: We performed standard 7-field stereoscopic fundus photography on 95 consecutive patients with type 1 and type 2 diabetes. Patients were categorized into 3 groups according to the presence or absence of DR and the duration of diabetes: group 1 was defined by presence of DR, group 2 was defined by absence of DR after >10 years duration of diabetes, and group 3 was defined by absence of DR with long-standing diabetes (> or =20 years for type 1 diabetes and > or =15 years for type 2 diabetes). Monocytes from 40 ml peripheral blood were isolated from all patients, and the hypoxic induction of VEGF was determined in vitro. RESULTS: We found no significant difference in the basal level of VEGF in patients with and without DR. However, we did find a markedly significant difference in the hypoxic induction of VEGF between patients from group 1 and group 3 (4.35+/-0.55 vs. 1.87+/-0.3, P<0.00013). CONCLUSIONS: This study suggests that 1 mechanism for the absence of DR in patients with long-standing diabetes is a decreased hypoxic induction of VEGF.
QT interval prolongation and mortality in type 1 diabetic patients: a 5-year cohort prospective study. Neuropathy Study Group of the Italian Society of the Study of Diabetes, Piemonte Affiliate.
Authors: Veglio M , Sivieri R , Chinaglia A , Scaglione L , Cavallo-Perin P
Published: March 2007

OBJECTIVE: The aim of the study was to assess the relationship between QT interval prolongation and mortality in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Data on survival after 5 years were obtained from 316 of 379 patients (83.3%) who took part in a study on the prevalence of diabetic neuropathy and QT interval prolongation. RESULTS: Mortality at 5 years was 6.32%. Patients who survived were significantly younger (P = 0.04), had a shorter duration of diabetes (P = 0.01), had lower systolic (P = 0.004) and diastolic (P = 0.03) blood pressure levels, and had a shorter QT interval corrected for the previous cardiac cycle length (QTc) (P = 0.000005) than subjects who died. In univariate analysis, patients had a higher risk of dying if they had a prolonged QTc (odds ratio [OR] 20.14 [95% CI 5.7-70.81) or if they were affected by autonomic neuropathy (3.55 [1.4-8.9]). QTc prolongation was the only variable that showed a significant mortality OR in multivariate analysis (24.6 [6.51-92.85]; P = 0.0000004). CONCLUSIONS: This is the first cohort-based prospective study indicating that QTc prolongation is predictive of increased mortality in type 1 diabetic patients.
Vitamin E supplementation restores glutathione and malondialdehyde to normal concentrations in erythrocytes of type 1 diabetic children.
Authors: Jain S K , McVie R , Smith T
Published: March 2007

OBJECTIVE: This study examined the relationship between cellular glutathione and vitamin E concentrations and the effect of vitamin E (alpha-tocopherol) supplementation on glutathione and lipid peroxidation product concentrations in the erythrocytes of type 1 diabetic patients. RESEARCH DESIGN AND METHODS: We obtained written informed consent to participate in this study from diabetic patients (n = 29) and their age-matched nondiabetic siblings (n = 21) according to the guidelines of the Institutional Review Board on Human Experimentation. Diabetic patients were supplemented with a DL-alpha-tocopherol (vitamin E) capsule (100 IU/orally) or placebo for 3 months in a double-blind clinical trial. Fasting blood samples were collected from each diabetic patient before the start of and after the 3 months of vitamin E or placebo supplementation. Glutathione, malondialdehyde (which is a product of lipid peroxidation), and alpha-tocopherol were determined using high-performance liquid chromatography A total of 5 diabetic patients were excluded after randomization from the data analyses. Data were analyzed statistically using a paired Students t test to compare 12 diabetic patients taking vitamin E with 12 diabetic patients receiving placebo supplementation and to compare diabetic patients with healthy nondiabetic subjects. RESULTS: Erythrocytes of diabetic patients had 21% higher (P<0.001) malondialdehyde and 15% lower (P<0.05) glutathione concentrations than healthy subjects. Vitamin E in erythrocytes had a significant correlation with the glutathione concentrations in the erythrocytes (r = 0.46, P<0.02). Vitamin E supplementation increased glutathione concentrations by 9% (P<0.01) and lowered concentrations of malondialdehyde by 23% (P<0.001) and of HbA1c by 16% (P<0.02) in erythrocytes of diabetic patients. No differences were evident in these parameters before versus after placebo supplementation. CONCLUSIONS: Glutathione level is significantly related to vitamin E level, and supplementation with vitamin E (100 IU/day) significantly increases glutathione and lowers lipid peroxidation and HbA1c concentrations in the erythrocytes of type 1 diabetic patients.
Flexible Meal-Related Dosing With Repaglinide Facilitates Glycemic Control in Therapy-Naive Type 2 Diabetes
Authors: Moses Robert G. , Gomis Ramon , Frandsen Kirstine Brown , Schlienger Jean-Louis , Dedov Ivan
Published: March 2007

OBJECTIVE— This double-blind randomized placebo-controlled parallel group study assessed the efficacy and safety (with particular regard to body weight and hypoglycemia) of repaglinide when used in a flexible mealtime dosing regimen in a situation close to everyday clinical practice.

RESEARCH DESIGN AND METHODS— A total of 408 patients with type 2 diabetes considered poorly controlled by diet, but without a history of previous antidiabetic medication, were randomized to receive 0.5 mg repaglinide at mealtimes (increased to 1 mg after 4 weeks depending on blood glucose response) or placebo for 16 weeks. Patients were free to choose a flexible meal pattern, adjusting the dosing schedule from two to four preprandial doses per day in accordance with a “one meal, one dose; no meal, no dose” principle. Additional snacks were not a requirement of the treatment schedule.

RESULTS— Treatment with repaglinide significantly improved glycemic control with respect to baseline and placebo, reducing HbAlc by 1.14% from baseline and fasting plasma glucose by 1.8 mmol/l. Improvement in glycemic control was independent of the meal pattern adopted by patients, including those most commonly taking two or four meals daily, with no correlation between meal pattern and risk of hypoglycemia. The improvement in glycemic control was also independent of degree of obesity and age ≤65 or >65 years. There was no significant body weight increase in the repaglinide group.

CONCLUSIONS— Mealtime dosing with repaglinide is effective in improving overall glycemic control in type 2 diabetic patients for which control is suboptimal using diet alone. Patients are able to vary their meal pattern from a conventional regimen of three meals daily without compromising control or increasing the risk of adverse events.
Efficacy, Safety, and Pump Compatibility of Insulin Aspart Used in Continuous Subcutaneous Insulin Infusion Therapy in Patients With Type 1 Diabetes
Authors: Bode Bruce W. , Strange Poul
Published: March 2007

OBJECTIVE— The purpose of this study was to compare the efficacy, safety, and pump compatibility of insulin aspart (a rapid-acting insulin analog) and buffered regular human insulin in patients with type 1 diabetes undergoing continuous subcutaneous insulin infusion (CSII)therapy.

RESEARCH DESIGN AND METHODS— This was a single-center randomized openlable study. Patients received CSII therapy with insulin aspart(n = 19) or buffered regular human insulin (n = 10) for 7 weeks. Bolus doses of insulin aspart were administered immediately before meals and buffered regular human insulin 30 min before meals.

RESULTS— Insulin aspart and buffered regular human insulin were both effective in controlling average daily blood glucose levels (8.2± 1.9 and 8.5 ± 2.1 mmol/l, respectively) (mean ± SD) and maintaining serum fructosamine (343 ± 25.7 and 336 ± 27.4μmol/l) and HbAlc (6.9 ± 0.6 and 7.1 ± 0.6 %)levels. Possible obstructions and set leakages were infrequently reported in both groups. Similar numbers of patients experienced hypoglycemia (blood glucose <2.5 mmol/l): 14 (74%) insulin aspart patients versus 6 (60%)buffered regular human insulin patients. Patients receiving insulin aspart had fewer hypoglycemic events per patient (2.9) than those patients receiving buffered regular human insulin (6.2). There were no differences between the two insulins in the occurrence of hyperglycemic events (blood glucose >19 mmol/l) or in the number and type of adverse events.

CONCLUSIONS— Insulin aspart and buffered regular human insulin were effective and well tolerated and provided similar pump compatibility when used in CSII therapy.
Insulin Resistance and Insulin Secretory Dysfunction Are Independent Predictors of Worsening of Glucose Tolerance During Each Stage of Type 2 Diabetes Development
Authors: Weyer Christian , Tataranni P. Antonio , Bogardus Clifton , Pratley Richard E.
Published: March 2007

OBJECTIVE— Although prospective studies indicate that insulin resistance and insulin secretory dysfunction predict type 2 diabetes, they provide limited information on the relative contributions of both abnormalities to worsening glucose tolerance at different developmental stages of the disease. We therefore assessed the predictive effect of insulin resistance and insulin secretory dysfunction separately for the progression from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) and from IGT to diabetes.

RESEARCH DESIGN AND METHODS— Insulin-stimulated glucose disposal (M) (hyperinsulinemic clamp), acute insulin secretory response (AIR) (25-g intravenous glucose tolerance test), and body composition(hydrodensitometry or dual-energy X-ray absorptiometry) were measured in 254 Pima Indians with NGT and in 145 Pima Indians with IGT, who were then followed for 0.5-13 years.

RESULTS— After follow-ups of 4.4 ± 3.1 and 5.5 ±3.4 years, 79 (31%) of the subjects with initial NGT had developed IGT, and 64(44%) of the subjects with initial IGT had developed diabetes. In proportional-hazards analyses with adjustment for age, sex, and percent body fat, low M and low AIR were independent predictors of both the progression from NGT to IGT (relative hazards [95% CI] for 10th vs. 90th percentile: M 2.4 [1.2-4.7], P < 0.02; AIR 2.1 [1.1-4.1], P < 0.04) and from IGT to diabetes (M 2.5 [1.3-5.0], P < 0.01; AIR 1.8 [0.99-3.3], P = 0.055).

CONCLUSIONS— During each stage of the development of type 2 diabetes, insulin resistance and insulin secretory dysfunction are independent predictors of worsening glucose tolerance and are, therefore, both targets for the primary prevention of the disease.
Postchallenge Hyperglycemia in a National Sample of U.S. Adults With Type 2 Diabetes
Authors: Erlinger Thomas P. , Brancati Frederick L.
Published: March 2007

OBJECTIVE—Postchallenge hyperglycemia (PCH) is known to contribute to suboptimal glycemic control in adults with non–insulin-requiring type 2 diabetes. The objective of this study was to estimate the prevalence of PCH among individuals with diabetes.

RESEARCH DESIGN AND METHODS—We conducted a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey (1988–1994) in adults aged 40–74 years with diabetes who were not using insulin (i.e., they used oral hypoglycemics or received no pharmacological therapy). Each respondent underwent a standard 75-g oral glucose tolerance test. PCH was defined as a 2-h glucose level ≥200 mg/dl.

RESULTS—Overall, PCH was present in 74% of those with diagnosed diabetes. Although it was present in virtually all (99%) of the diabetic adults under suboptimal glycemic control (HbA1c ≥7.0%), PCH was also common (39%) among those under optimal control (HbA1c <7.0%). Likewise, among sulfonylurea users, PCH was present in 99% of those under suboptimal control and in 63% of those under good control. Similar patterns were observed in those with undiagnosed diabetes. Isolated PCH (2-h glucose ≥200 mg/dl and fasting glucose <126 mg/dl) was present in 9.8% of the adults with diagnosed diabetes.

CONCLUSIONS—These data suggest that PCH is common among diabetic adults in the U.S., even in the setting of “optimal” glycemic control and sulfonylurea use. Interventions designed to lower postprandial glucose excursions may help improve overall glycemic control in the general population of U.S. adults with diabetes.
Mediators of Lifestyle Behavior Change in Native Hawaiians
Authors: Mau Marjorie K. , Glanz Karen , Severino Richard , Grove John S. , Johnson Bruce , Curb J. David
Published: March 2007

OBJECTIVE—To examine the association of stage of change with diet and exercise behaviors in response to a lifestyle intervention for Native Hawaiians (NHs).

RESEARCH DESIGN AND METHODS—A family (‘ohana) support lifestyle intervention was compared with a standard intervention in NHs with or at risk for diabetes in two rural communities in Hawaii (n = 147). Stage of change, as a hypothesized mediator of behavior change, and dietary and exercise behaviors were measured at baseline and at 1 year postintervention.

RESULTS—Stage of change was significantly associated with positive dietary and exercise behaviors. NHs receiving the ‘ohana support (OS) intervention were more likely to advance from pre-action to action/maintenance for fat intake and physical activity than the group who received the standard intervention. Participants in the OS group who advanced from pre-action to action/maintenance showed more improvement in fat intake and physical activity than those in the standard group.

CONCLUSIONS—These initial findings suggest that stage of change is an important factor in mediating lifestyle behavior changes in persons with or at risk for diabetes and merits further study among minority populations at high risk for diabetes.
Clinical Efficacy of Fidarestat, a Novel Aldose Reductase Inhibitor, for Diabetic Peripheral Neuropathy
Authors: Hotta Nigishi , Toyota Takayoshi , Matsuoka Kempei , Shigeta Yukio , Kikkawa Ryuichi , Kaneko Toshio , Takahashi Akira , Sugimura Kimiya , Koike Yasuo , Ishii Jun , Sakamoto Nobuo ,   The SNK-860 Diabetic Neuropathy Study Group
Published: March 2007

OBJECTIVE—The purpose of this study was to evaluate the efficacy of fidarestat, a novel aldose reductase (AR) inhibitor, in a double-blind placebo controlled study in patients with type 1 and type 2 diabetes and associated peripheral neuropathy.

RESEARCH DESIGN AND METHODS—A total of 279 patients with diabetic neuropathy were treated with placebo or fidarestat at a daily dose of 1 mg for 52 weeks. The efficacy evaluation was based on change in electrophysiological measurements of median and tibial motor nerve conduction velocity, F-wave minimum latency, F-wave conduction velocity (FCV), and median sensory nerve conduction velocity (forearm and distal), as well as an assessment of subjective symptoms.

RESULTS—Over the course of the study, five of the eight electrophysiological measures assessed showed significant improvement from baseline in the fidarestat-treated group, whereas no measure showed significant deterioration. In contrast, in the placebo group, no electrophysiological measure was improved, and one measure significantly deteriorated (i.e., median nerve FCV). At the study conclusion, the fidarestat-treated group was significantly improved compared with the placebo group in two electrophysiological measures (i.e., median nerve FCV and minimal latency). Subjective symptoms (including numbness, spontaneous pain, sensation of rigidity, paresthesia in the sole upon walking, heaviness in the foot, and hypesthesia) benefited from fidarestat treatment, and all were significantly improved in the treated versus placebo group at the study conclusion. At the dose used, fidarestat was well tolerated, with an adverse event profile that did not significantly differ from that seen in the placebo group.

CONCLUSIONS—The effects of fidarestat-treatment on nerve conduction and the subjective symptoms of diabetic neuropathy provide evidence that this treatment alters the progression of diabetic neuropathy.
The Effect of Evening Alcohol Consumption on Next-Morning Glucose Control in Type 1 Diabetes
Authors: Turner Benjamin C. , Jenkins Emma , Kerr David , Sherwin Robert S. , Cavan David A.
Published: March 2007

OBJECTIVE—Alcohol is associated with acute hypoglycemia in patients with type 1 diabetes. After drinking alcohol in the evening, delayed hypoglycemia has also been described, although its cause is unknown. We performed a controlled study to investigate this phenomenon.

RESEARCH DESIGN AND METHODS—We admitted six men with type 1 diabetes (aged 19–51 years, HbA1c 7.0–10.3%) on two occasions, from 5:00 p.m. to 12:00 noon the following day. They received regular insulin injections before standardized meals, at 6:00 p.m. and 8:00 a.m., and a basal insulin infusion (0.15 mU · kg−1 · min−1) from 11:00 p.m. They drank either dry white wine (0.75 g/kg alcohol) or mineral water at 9:00 p.m. over 90 min. Blood glucose, alcohol, insulin, cortisol, growth hormone, and glucagon levels were measured.

RESULTS—Blood ethanol reached a mean (SEM) peak of 19.1 (1.2) mmol/l and was undetectable by 8:00 a.m. There were no significant differences in evening or overnight blood glucose levels between the studies. In the morning, fasting and postprandial blood glucose levels were significantly lower after consumption of wine (postprandial peak 8.9 [1.7] vs. 15 [1.5] mmol/l, P < 0.01), and from 10:00 a.m., five subjects required treatment for hypoglycemia (nadir 1.9–2.9 mmol/l). None of the subjects had hypoglycemia after consumption of water. After consumption of wine, growth hormone secretion was significantly reduced between midnight and 4:00 a.m. (area under the curve 2.1 [1.1] vs. 6.5 [2.1] μg · l–1 · h–1, P = 0.04). There were no differences in insulin or other hormone levels.

CONCLUSIONS—In type 1 diabetes, moderate consumption of alcohol in the evening may predispose patients to hypoglycemia after breakfast the next morning. This is associated with reduced nocturnal growth hormone secretion. Patients should be informed of this risk and advised regarding appropriate preventative measures.
Projection of Diabetes Burden Through 2050
Authors: Boyle James P. , Honeycutt Amanda A. , Narayan K.M. Venkat , Hoerger Thomas J. , Geiss Linda S. , Chen Hong , Thompson Theodore J.
Published: March 2007

OBJECTIVE—To project the number of people with diagnosed diabetes in the U.S. through 2050, accounting for changing demography and diabetes prevalence rates.

RESEARCH DESIGN AND METHODS—We combined age-, sex-, and race-specific diagnosed diabetes prevalence rates—predicted from 1980–1998 trends in prevalence data from the National Health Interview Survey—with Bureau of Census population demographic projections. Sensitivity analyses were performed by varying both prevalence rate and population projections.

RESULTS—The number of Americans with diagnosed diabetes is projected to increase 165%, from 11 million in 2000 (prevalence of 4.0%) to 29 million in 2050 (prevalence of 7.2%). The largest percent increase in diagnosed diabetes will be among those aged ≥75 years (+271% in women and +437% in men). The fastest growing ethnic group with diagnosed diabetes is expected to be black males (+363% from 2000–2050), with black females (+217%), white males (+148%), and white females (+107%) following. Of the projected 18 million increase in the number of cases of diabetes in 2050, 37% are due to changes in demographic composition, 27% are due to population growth, and 36% are due to increasing prevalence rates.

CONCLUSIONS—If recent trends in diabetes prevalence rates continue linearly over the next 50 years, future changes in the size and demographic characteristics of the U.S. population will lead to dramatic increases in the number of Americans with diagnosed diabetes.