Fasting Plasma Glucose Concentrations Research Articles

Regional body fat distribution and metabolic profile in postmenopausal women

The aim of the study was to examine how body fat distribution variables were associated with metabolic parameters in a sample of 113 postmenopausal women not receiving hormone therapy (56.9 ± 4.4 years, 28.4 ± 5.1 kg/m 2). Body fat distribution variables (visceral adipose tissue [AT], subcutaneous AT, and total midthigh AT) were measured using computed tomography; body fat mass was assessed by hydrostatic weighing; insulin sensitivity was determined with the euglycemic-hyperinsulinemic clamp; fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) concentrations were measured by a 75-g oral glucose load; and (high-sensitivity) C-reactive protein (hs-CRP) was measured using a highly sensitive assay. After controlling for fat mass, visceral AT was positively associated with plasma triglyceride, hs-CRP, FPG, and 2hPG, and negatively associated with high-density lipoprotein cholesterol (HDL-C) and insulin sensitivity. Total midthigh AT was negatively associated with apolipoprotein B, FPG, and 2hPG, and positively associated with insulin sensitivity. Stepwise multiple regression analyses including abdominal visceral AT, subcutaneous AT and total midthigh AT as independent variables showed that abdominal visceral AT best predicted the variance in plasma triglyceride, HDL-C, low-density lipoprotein peak particle size, hs-CRP, FPG, 2hPG, and insulin sensitivity. Abdominal subcutaneous AT was a significant predictor of only insulin sensitivity, whereas total midthigh AT predicted HDL-C, low-density lipoprotein peak particle size, and apolipoprotein B. These multivariate analyses also indicated that total midthigh AT was favorably related to these outcomes, whereas abdominal visceral AT and subcutaneous AT were unfavorably related. These results confirmed that abdominal visceral fat is a critical correlate of metabolic parameters in postmenopausal women. In addition, a higher proportion of AT located in the total midthigh depot is associated with a favorable metabolic profile.

Renal Function and Glucose Transport in Male and Female Mice with Diet-Induced Type II Diabetes Mellitus

Abstract. The aim of this study was to measure cardiovascular and renal function, including the renal transport capacity for glucose, in male and female C57BL/6J mice with diet-induced Type II diabetes mellitus. Typical of Type II diabetes, mice fed a high-fat, high-simple carbohydrate diet for 3 months were obese (45–65 g), hyperglycemic (138–259 mg%), and hyperinsulinemic (1.8–15.06 ng/ml); significant gender differences were observed in all cases. Based on systolic pressure measurements in conscious mice and arterial blood pressure measurements in anesthetized mice, no diet-induced hypertension was observed in either male or female mice. Urine flow rate, sodium, potassium, osmolar, and protein excretion rates were significantly increased (P < 0.05) in male mice fed the high-fat, high-simple carbohydrate diet compared with female mice fed the same diet. However, no differences in the excretion variables existed between male and female mice fed the control diet. The glomerular filtration rate (ml min−1 g kw−1), determined by FITC-inulin, in male and female mice fed the control diet (0.87 ± 0.01 and 0.90 ± 0.1, respectively) and high-fat, high-simple carbohydrate diet (0.96 ± 0.1 and 0.93 ± 0.2, respectively) was not different between the groups. These hyperglycemic mice were also not glucosuric. Infusions of progressive amounts of glucose in male mice fed either diet for 3 or 6 months demonstrated that the renal threshold for glucose was 400 mg% for all these mice, well above the fasting plasma glucose concentrations observed in this study. Thus, C57BL/6J mice were valuable tools for studying diet-induced obesity, hyperglycemia, and hyperinsulinemia; however, no hypertension or kidney dysfunction was apparent within the time frame of the current study.

Prevalence and associated factors of diabetic retinopathy. The Beijing Eye Study 2006

To evaluate the prevalence and associated factors of diabetic retinopathy in adult Chinese with diabetes mellitus. The Beijing Eye Study 2006 is a population-based cross-sectional study that included 3,251 (73.2%) subjects (aged 45+ years) out of 4,439 subjects originally participating in the Beijing Eye Study 2001. Diabetes defined as fasting glucose concentrations > or = 7.0 mmol/L or self-reported diagnosis of diabetes was detected in 381/3,251 (12.9%) subjects. Diabetic retinopathy was defined by the presence of at least one microaneurysm in the diabetic subjects according to the Early Treatment of Diabetic Retinopathy Study (ETDRS). Gradable fundus photographs were available for 362 (95.0%) subjects. Diabetic retinopathy was detected in 101 subjects (27.9%). Most of the diabetic retinopathy was of the mild type (74/101; 73%). Severe non-proliferative or proliferative diabetic retinopathy was present in 16 (16%) subjects, and clinically significant macular edema in four (4%) subjects. Presence of diabetic retinopathy was significantly associated with rural region (Odds ratio (OR): 3.52), duration of diabetes mellitus (OR: 1.08), fasting plasma glucose concentration (OR: 1.14), type of diabetes treatment (OR: 2.09), and marginally significantly, with hyperopic refractive error (OR: 1.13; P = 0.08). The stage of diabetic retinopathy was associated with rural region (P < 0.001), known duration of diabetes (P = 0.001), type of diabetes treatment (P = 0.001), concentrations of high-density lipoproteins (P = 0.004), and fasting glucose concentrations (P = 0.002). Prevalence of diabetic retinopathy among adult diabetic Chinese was about 27.9%. The stage of retinopathy was mild in 75% of the subjects with diabetic retinopathy. Associated factors were diabetes duration, diabetic treatment type, low metabolic control, rural region, and marginally hyperopia.

Plasma retinol-binding protein is not a marker of insulin resistance in overweight subjects: A three year longitudinal study

Objectives This longitudinal study investigated whether or not plasma retinol-binding protein (RBP), recently referred to as RBP4, was a marker of insulin resistance in overweight subjects. Methods We measured anthropometric markers as well as RBP, fasting glucose and insulin in 206 overweight subjects and repeated these measurements 36 months later. Subjects were grouped according to fasting plasma glucose concentration at baseline and 36 months. Results Subjects ( n = 51) with a normal basal fasting glucose (< 5.6 mmol/L) who developed impaired fasting glucose (IFG) 3 years later (≥ 5.6 mmol/L) showed a highly significant increase in both fasting insulin and insulin resistance, but importantly no change in plasma RBP. This group had a significant increase in body mass index (BMI). Subjects ( n = 101) with a normal fasting glucose at both baseline (< 5.6 mmol/L) and 36 months showed no significant change in fasting insulin, insulin resistance, RBP or BMI. The remaining subjects had impaired basal fasting glucose and were not analysed on a group-wise basis. Overall, RBP correlated significantly, but inversely, with anthropometric measures, but not with fasting glucose, insulin or insulin resistance. Conclusions This is the first report of a long-term longitudinal study on RBP and the major finding is that subjects who developed insulin resistance showed no change in plasma RBP. On the basis of our results we consider that RBP cannot be construed as a marker of insulin resistance in overweight humans.

Prevalence of subclinical hypothyroidism in patients with chronic kidney disease.

Subclinical primary hypothyroidism is highly prevalent in the general population, especially in the elderly. However, the prevalence of subclinical primary hypothyroidism in persons with chronic kidney disease (CKD) not requiring chronic dialysis is not well defined. Cross-sectional data from 3089 adult outpatients, who were consecutively referred by general practitioners for routine blood testing over the last two years, were analyzed. Glomerular filtration rate (GFR) was estimated by the abbreviated Modification of Diet in Renal Disease equation. Multivariable logistic regression was used to evaluate the independent association between prevalent subclinical primary hypothyroidism and estimated GFR. Among 3089 adult participants, 293 (9.5%) had subclinical primary hypothyroidism and 277 (9%) had an estimated GFR <60 ml/min per 1.73 m(2). The prevalence of subclinical primary hypothyroidism increased from 7% at an estimated GFR >or=90 ml/min per 1.73 m(2) to 17.9% at an estimated GFR <60 ml/min per 1.73 m(2) (P < 0.0001 for trend). Compared with participants with an estimated GFR >or=60 ml/min per 1.73 m(2), those with estimated GFR <60 ml/min per 1.73 m(2) had an increased odds of subclinical primary hypothyroidism after adjusting for age, gender, fasting plasma glucose, total cholesterol, and triglyceride concentrations. These findings suggest that subclinical primary hypothyroidism is a relatively common condition ( approximately 18%) among persons with CKD not requiring chronic dialysis, and it is independently associated with progressively lower estimated GFR in a large cohort of unselected outpatient adults.

Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects

Lignans, derived from flaxseed, are phyto-oestrogens being increasingly studied for their health benefits. An 8-week, randomised, double-blind, placebo-controlled study was conducted in fifty-five hypercholesterolaemic subjects, using treatments of 0 (placebo), 300 or 600 mg/d of dietary secoisolariciresinol diglucoside (SDG) from flaxseed extract to determine the effect on plasma lipids and fasting glucose levels. Significant treatment effects were achieved (P < 0.05 to < 0.001) for the decrease of total cholesterol (TC), LDL-cholesterol (LDL-C) and glucose concentrations, as well as their percentage decrease from baseline. At weeks 6 and 8 in the 600 mg SDG group, the decreases of TC and LDL-C concentrations were in the range from 22.0 to 24.38 % respectively (all P < 0.005 compared with placebo). For the 300 mg SDG group, only significant differences from baseline were observed for decreases of TC and LDL-C. A substantial effect on lowering concentrations of fasting plasma glucose was also noted in the 600 mg SDG group at weeks 6 and 8, especially in the subjects with baseline glucose concentrations > or = 5.83 mmol/l (lowered 25.56 and 24.96 %; P = 0.015 and P = 0.012 compared with placebo, respectively). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED) and enterolactone were all significantly raised in the groups supplemented with flaxseed lignan. The observed cholesterol-lowering values were correlated with the concentrations of plasma SECO and ED (r 0.128-0.302; P < 0.05 to < 0.001). In conclusion, dietary flaxseed lignan extract decreased plasma cholesterol and glucose concentrations in a dose-dependent manner.

Population Exposure‐Response Modeling of Metformin in Patients With Type 2 Diabetes Mellitus

The exposure-response properties of metformin were characterized in 12 subjects with type 2 diabetes mellitus. The time course of drug concentration and effects on fasting plasma glucose and lactic acid concentrations were used from a study in which subjects received 500 mg of metformin twice daily for 5 days followed by 850 mg twice daily for 5 days. Pharmacokinetic sampling included morning trough concentrations obtained on days 7 to 9 and rich sampling (15 time points) on day 10. Fasting plasma glucose and lactic acid concentrations were measured on days 0 to 10 and served as biomarkers of therapeutic effect and tolerability, respectively. A population pharmacokinetic/pharmacodynamic analysis was conducted using nonlinear mixed effects modeling. Metformin pharmacokinetics were described using a 1-compartment model with first-order absorption. Population mean estimates (relative standard error [RSE]) of clearance (CL/F) and volume of distribution were 79.0 L.h(-1) (6.8%) and 648 L (13.8%), respectively. Covariate analyses revealed that creatinine clearance (CL(CR)) significantly influenced metformin CL/F [CL/F = 79.0.(CL(CR)/80)(0.822)]. An indirect response model was applied to describe the antihyperglycemic effect of metformin. Population mean estimates (RSE) of baseline fasting plasma glucose and the drug concentration producing half-maximal effect were 241 mg.dL(-1) (4.6%) and 4.23 mg.L(-1) (31.0%). An empirical linear model was used to describe a slight progressive increase in fasting lactic acid during metformin treatment with an estimated slope coefficient (RSE) of 0.0005 mM.mL.ng(-1) (38.1%). Model evaluation by predictive check and nonparametric bootstrap analysis suggested that the proposed model is robust, and parameter values were estimated with good precision. Simulations suggested that the clinical utility of metformin was maintained over the dose range evaluated with respect to fasting plasma glucose and lactic acid response.

Effects of Exercise and Serum Uric Acid on the Metabolic Syndrome for Japanese Workers

The effects of exercise and serum uric acid on the metabolic syndrome (MetS) were evaluated. The study subjects were 1792 Japanese male workers aged 21 to 60 years old who were employees of a manufacturing company of electrical products. The standard Japanese criteria for the diagnosis of MetS were used. The presence of obesity is an indispensable factor, with any two or more of the following criteria: (1) a high serum level of triglyceride and/or low serum level of HDL cholesterol; (2) high blood pressure; (3) high fasting plasma glucose concentration. The body mass index (BMI) was used as an obesity-related overweight index; BMI >or=25 kg/m(2) was defined as overweight. Age, smoking habit and frequency of drinking were used for the adjustment of significance. The odds ratios (95% confidence intervals) of serum uric acid >or=7 mg/dL, and no history of exercise for MetS were 3.2 (2.2, 4.6) and 1.8 (1.1, 3.0), respectively. The authors also categorized walking by the number of steps per day and by the time in minute per day. Although subjects with no habitual exercise have risk of MetS, the situation of physical activity should precisely be evaluated.

Effects of barnidipine on blood pressure and left ventricular diastolic function in patients with hypertension and metabolic syndrome: A 12-week, open-label noncomparison study

Background: Barnidipine is one of a new generation of dihydropyridine calcium-channel blockers. Despite evidence of favorable effects on blood pressure (BP) and insulin sensitivity, this drug has rarely been tested in hypertensive patients with metabolic syndrome (MS). Objective: The aim of this study was to evaluate the effects of barnidipine on BP and left ventricular (LV) diastolic function in patients with hypertension and MS. Methods: Consecutive subjects aged 18 to 75 years with systolic BP (SBP) of 140 to 179 mm Hg and/or diastolic BP (DBP) of 90 to 109 mm Hg and MS (based on Adult Treatment Panel III criteria) were assessed for inclusion in the study. Lifestyle changes according to current guidelines were recommended and barnidipine monotherapy 10 mg daily was initiated. All patients entered a 2-week run-in period. After a 6-week treatment period, the daily dosage was doubled for the remainder of the study in patients whose BP remained uncontrolled (≥140/≥90 mm Hg). We assessed the glycolipidic profile and LV structure and function using standard Doppler and tissue Doppler imaging (TDI) echocardiography before and after 12 weeks of treatment. Ambulatory BP records and electrocardiographic and echocardiographic tracings were coded and shipped to a central laboratory for blinded analysis. Possible adverse events (AEs) were recorded at predetermined intervals throughout the follow-up period and at unplanned intervals whenever an AE became known to the investigators. Results: Thirty-four consecutive patients were assessed for inclusion. Thirty consecutive patients (20 men, 10 women; mean {SD| age, 55.9 {10.3| years; 5 current smokers) were included in the study. At study entry, mean office SBP was 146 mm Hg, DBP was 87 mm Hg, and heart rate was 72 beats/min. At the study end, mean office SBP/DBP was <140/90 mm Hg in 20 patients (66.7%). From baseline to study end, 24-hour ambulatory BP decreased significantly by 12 and 8 mm Hg for SBP and DBP, respectively (both, P = 0.001). The smoothness index was 0.92 for SBP and 0.82 for DBP. Fasting plasma glucose concentration decreased significantly from 110 to 104 mg/dL ( P = 0.001). Total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol concentrations did not change significantly. From baseline to study end, there were no significant changes in LV structure or systolic function (LV mass, 50.7 vs 50.6 g/ht 2.7; LV diastolic/systolic diameters, 47.50/29.80 vs 48.40/30.76 mm; wall motion score index, 1.0 vs 1.0; ejection fraction, 61% vs 60%), while the peak E/A velocity ratio on TDI increased from 1.078 to 1.245 ( P = 0.009). No AEs (including AEs reflected by chemistry values) either unrelated or related to treatment were noted during the 12-week duration of the study. Conclusions: In these hypertensive patients with MS, a 12-week treatment period with barnidipine in addition to lifestyle modifications was associated with significant reductions in 24-hour BP and BP variability, reduction in plasma glucose concentration, and improvement in LV diastolic relaxation. No significant changes in lipid concentrations, LV structure, or systolic function were found.

High Plasma Retinol Binding Protein-4 and Low Plasma Adiponectin Concentrations Are Associated with Severity of Glucose Intolerance in Women with Previous Gestational Diabetes Mellitus

Women with previous gestational diabetes mellitus (pGDM) are at high risk of developing type 2 diabetes mellitus in the future. The role of adipokines in women with pGDM has not been established. We investigated whether circulating adipokine concentration is associated with abnormal glucose homeostasis in women with pGDM. DESIGN, SETTING, PATIENTS, AND MAIN OUTCOME MEASURES: We measured the plasma concentrations of retinol-binding protein-4 (RBP4), transthyretin (TTR), and adiponectin and metabolic parameters in four groups of women who exhibited normal glucose tolerance (NGT) during a previous pregnancy (NP, n = 17), NGT after GDM (GDM-NGT, n = 72), impaired glucose tolerance after GDM (GDM-IGT, n = 60), and type 2 diabetes after GDM (GDM-DM, n = 8). Plasma RBP4 concentration was significantly higher in women with GDM-DM, GDM-IGT, and GDM-NGT than in those with NP. RBP4 concentration correlated positively with TTR concentration; fasting plasma glucose, insulin, and triglyceride concentrations; blood pressure; abdominal fat area; and homeostasis model assessment of insulin resistance. Plasma TTR concentration was elevated in women with GDM-DM compared with other groups. In contrast, adiponectin concentration was lowest in the GDM-DM group and correlated inversely with parameters of insulin resistance. Resistin concentration was higher only in the GDM-NGT and GDM-IGT groups, whereas leptin did not differ between groups. Plasma RBP4 and adiponectin concentrations were inversely correlated. The severity of glucose intolerance in women with pGDM is associated with high RBP4 and low adiponectin concentrations.

Effect of cinnamon and turmeric on urinary oxalate excretion, plasma lipids, and plasma glucose in healthy subjects

BackgroundHigh oxalate intake resulting from consuming supplemental doses of cinnamon and turmeric may increase risk of hyperoxaluria, a significant risk factor for urolithiasis. ObjectiveThis study assessed urinary oxalate excretion from supplemental doses of cinnamon and turmeric as well as changes in fasting plasma glucose, cholesterol, and triacylglycerol concentrations. DesignEleven healthy subjects, aged 21–38 y, participated in an 8-wk, randomly assigned, crossover study that involved the ingestion of supplemental doses of cinnamon and turmeric for 4-wk periods that provided 55 mg oxalate/d. Oxalate load tests, which entailed the ingestion of a 63-mg dose of oxalate from the test spices, were performed after each 4-wk experimental period and at the study onset with water only (control treatment). Fasting plasma glucose and lipid concentrations were also assessed at these time points. ResultsCompared with the cinnamon and control treatments, turmeric ingestion led to a significantly higher urinary oxalate excretion during the oxalate load tests. There were no significant changes in fasting plasma glucose or lipids in conjunction with the 4-wk periods of either cinnamon or turmeric supplementation. ConclusionsThe percentage of oxalate that was water soluble differed markedly between cinnamon (6%) and turmeric (91%), which appeared to be the primary cause of the greater urinary oxalate excretion/oxalate absorption from turmeric. The consumption of supplemental doses of turmeric, but not cinnamon, can significantly increase urinary oxalate levels, thereby increasing risk of kidney stone formation in susceptible individuals.

Effects of 18α-glycyrrhizin on the pharmacodynamics and pharmacokinetics of glibenclamide in alloxan-induced diabetic rats

This paper investigated the effects of 18α-glycyrrhizin (18α-GL) on the pharmacodynamics and pharmacokinetics of glibenclamide in experimental diabetic rats. 18α-GL (25 mg/kg) and/or glibenclamide (1 mg/kg) were given to alloxan-induced diabetic rats for consecutive 5 days. When the rats were co-treated with 18α-GL and glibenclamide, fasting plasma glucose concentration was further reduced, plasma insulin content and liver glycogen level were increased markedly as compared with glibenclamide-treated animals. Meanwhile, in co-treated group, elimination rate constant (Ke) of glibenclamide was reduced while peak plasma concentration ( C max), area under the plasma concentration vs time curve (AUC 0–14 h) and elimination half-life ( T 1/2Ke) were increased significantly vs glibenclamide alone administered rats. The activities of hepatic CYP3A and the markers of liver injury, plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly decreased in rats treated with 18α-GL alone and in combination with glibenclamide. Results of immunohistochemistry showed that 18α-GL improved the effects of glibenclamide on the pathological morphology of pancreatic islet β cells and the intensities of positive immunostaining for insulin. Our results revealed that 18α-GL led to the enhancement of the hypoglycemic effect of glibenclamide by inhibiting the activity of CYP3A; on the other hand, 18α-GL protected the pancreatic islet β cells and liver from damage in diabetes which suggested that 18α-GL might be beneficial as an adjuvant drug of glibenclamide in a proper dose, especially to the diabetic patients associated with liver dysfunction.

Glucagon and hyperglycaemia in diabetes

Glucagon, in the setting of absolute or relative insulin deficiency, is thought to contribute to the pathogenesis of hyperglycaemia in diabetes, but much of the evidence is extrapolated from short-term studies to the long-term condition. In the present issue of Clinical Science, Li and co-workers report that infusion of glucagon raised fasting plasma glucose concentrations and impaired glucose tolerance over 4 weeks in mice, thus demonstrating a sustained glycaemic effect of hyperglucagonaemia. Nonetheless, compelling evidence that glucagon contributes to the pathogenesis of hyperglycaemia in diabetes awaits long-term selective reduction of glucagon secretion or action in humans.

Sex Differences in Diabetes Risk and the Effect of Intensive Lifestyle Modification in the Diabetes Prevention Program

OBJECTIVE—In participants of the Diabetes Prevention Program (DPP) randomized to intensive lifestyle modification (ILS), meeting ILS goals strongly correlated with prevention of diabetes in the group as a whole. Men met significantly more ILS goals than women but had a similar incidence of diabetes. Therefore, we explored sex differences in risk factors for diabetes and the effect of ILS on risk factors.RESEARCH DESIGN AND METHODS—Baseline risk factors for diabetes and percent change in risk factors over the first year in men versus women were compared using Wilcoxon's rank-sum tests.RESULTS—At baseline, men were older and had a larger waist circumference; higher fasting plasma glucose concentration, caloric intake, and blood pressure; and lower HDL cholesterol and corrected insulin response than women, who were less physically active and had a higher BMI (P < 0.01 for all comparisons). Over the first year of the DPP, no sex difference in risk factors for diabetes was observed for those who lost <3% body weight. Weight loss of 3–7% body weight yielded greater decreases in 2-h glucose (P < 0.01), insulin concentration (P < 0.04), and insulin resistance (P < 0.03) in men than in women. Weight loss of >7% body weight resulted in greater decreases in 2-h glucose (P < 0.01), triglyceride level (P < 0.01), and A1C (P < 0.03) in men than in women.CONCLUSIONS—Weight loss >3% body weight yielded greater reduction in risk factors for diabetes in men than in women. Despite the more favorable effects of ILS in men, baseline risk factors were more numerous in men and likely obscured any sex difference in incident diabetes.

Common Variants in Maturity-Onset Diabetes of the Young Genes and Future Risk of Type 2 Diabetes

Mutations in the hepatocyte nuclear factor (HNF)-1alpha, HNF-4alpha, glucokinase (GCK), and HNF-1beta genes cause maturity-onset diabetes of the young (MODY), but it is not known whether common variants in these genes predict future type 2 diabetes. We tested 14 previously associated polymorphisms in HNF-1alpha, HNF-4alpha, GCK, and HNF-1beta for association with type 2 diabetes-related traits and future risk of type 2 diabetes in 2,293 individuals from the Botnia study (Finland) and in 15,538 individuals from the Malmö Preventive Project (Sweden) with a total follow-up >360,000 years. The polymorphism rs1169288 in HNF-1alpha strongly predicted future type 2 diabetes (hazard ratio [HR] 1.2, P = 0.0002). Also, SNPs rs4810424 and rs3212198 in HNF-4alpha nominally predicted future type 2 diabetes (HR 1.3 [95% CI 1.0-1.6], P = 0.03; and 1.1 [1.0-1.2], P = 0.04). The rs2144908 polymorphism in HNF-4alpha was associated with elevated rate of hepatic glucose production during a hyperinsulinemic-euglycemic clamp (P = 0.03) but not with deterioration of insulin secretion over time. The SNP rs1799884 in the GCK promoter was associated with elevated fasting plasma glucose (fPG) concentrations that remained unchanged during the follow-up period (P = 0.4; SE 0.004 [-0.003-0.007]) but did not predict future type 2 diabetes (HR 0.9 [0.8-1.0], P = 0.1). Polymorphisms in HNF-1beta (transcription factor 2 [TCF2]) did not significantly influence insulin or glucose values nor did they predict future type 2 diabetes. In conclusion, genetic variation in both HNF-1alpha and HNF-4alpha predict future type 2 diabetes, whereas variation in the GCK promoter results in a sustained but subtle elevation of fPG that is not sufficient to increase risk for future type 2 diabetes.

Predictors of glycemic control in Japanese subjects with type 2 diabetes mellitus

The purpose of this study was to investigate which pathophysiological and demographic characteristics of Japanese subjects with type 2 diabetes mellitus were associated with poor glycemic control and to propose a statistical model for predicting their glycemic control. A total of 220 subjects with type 2 diabetes mellitus were enrolled in this study. Frequently sampled intravenous glucose tolerance test was performed to determine the first-phase C-peptide secretion rate (CS1) and insulin sensitivity index. Multiple regression analysis in a stepwise manner was carried out to identify independent regulators of glycemic control. Upon stepwise linear regression analysis with hemoglobin A 1c as a dependent parameter, fasting plasma glucose concentration (FPG), CS1, and onset age remained as predictors, explaining 41.0% of glycemic control. The young-onset group (onset age ≤48 years) had significantly higher hemoglobin A 1c than the old-onset group (onset age >48 years) ( P = .0148), although the present age was significantly older in the old-onset group; and there were no significant differences in duration of diabetes, treatment, body mass index, FPG, fasting insulin level, homeostasis model assessment of insulin resistance, CS1, and log(insulin sensitivity index) between them. Worsening factors of glycemic control in Japanese subjects with type 2 diabetes mellitus were elevated FPG, impaired first-phase insulin secretion, and young age of onset of the disease. Because glycemic control in the subjects with young-onset diabetes tends to be worse, early and aggressive intervention should be required for those with young-onset diabetes to prevent long-term complications.

The common rs9939609 gene variant of the fat mass- and obesity-associated gene FTO is related to fat cell lipolysis

We investigated the rs9939609 single nucleotide polymorphism of the FTO gene in relation to fat cell function and adipose tissue gene expression in 306 healthy women with a wide range in body mass index (18-53 kg/m(2)). Subcutaneous adipose tissue biopsies were taken for fat cell metabolism studies and in a subgroup (n = 90) for gene expression analyses. In homozygous carriers of the T-allele, the in vitro basal (spontaneous) adipocyte glycerol release was increased by 22% (P = 0.007) and the in vivo plasma glycerol level was increased by approximately 30% (P = 0.037) compared with carriers of the A allele. In contrast, there were no genotype effects on catecholamine-stimulated lipolysis or basal or insulin-induced lipogenesis. We found no difference between genotypes for adipose tissue mRNA levels of FTO, hormone-sensitive lipase, adipose triglyceride lipase, perilipin, or CGI-58. Finally, the adipose tissue level of FTO mRNA was increased in obesity (P = 0.002), was similar in subcutaneous and omental adipose tissue, was higher in fat cells than in fat tissue (P = 0.0007), and was induced at an early stage in the differentiation process (P = 0.004). These data suggest a role of the FTO gene in fat cell lipolysis, which may be important in explaining why the gene is implicated in body weight regulation.

Inclusion of Educational Messages in Laboratory Reports Aids to Complete the Diagnostic Workup of Hyperglycemia

To evaluate whether educational messages regarding oral glucose tolerance test (OGTT) indications in laboratory reports increase the number of OGTTs appropriately requested. The following message was printed on the lab reports of individuals with a fasting plasma glucose (FPG) concentration between 5.5 and 6.9 mmol/l: "A FPG between 5.5 and 6.9 mmol/l is considered abnormal by the American Diabetes Association (impaired fasting glucose). An OGTT is recommended if the patient does not have a diagnosis of diabetes and suffers from conditions associated with an increased risk for having type 2 diabetes (i.e., overweight, high blood pressure, abnormal plasma lipids or family history of diabetes)." The number of educational messages printed was 81,099. The intervention resulted in a significant increase in the number of OGTTs requested, from 78 +/- 19 to 268 +/- 48 tests per month. It also resulted in a greater proportion of case subjects that had an abnormal OGTT result. Educational messages in laboratory reports aid in the diagnostic workup of hyperglycemia.

Ocular and systemic factors associated with diabetes mellitus in the adult population in rural and urban China. The Beijing Eye Study

To assess ocular and systemic factors associated with diabetes mellitus in the adult population in rural and urban China. The Beijing Eye Study 2006, a population-based, cross-sectional cohort study, included 3251 subjects aged 45 years and more (participation rate: 73.2%). Blood samples were available for 2960 (91.0%) subjects. Diabetes mellitus was defined by a fasting plasma glucose concentration >or=7.0 mmol/l or by a self-reported history diagnosis of diabetes. Diabetes mellitus was found in 381 (12.9%) subjects. In binary regression analysis, the presence of diabetes mellitus was significantly associated with body mass index, systolic blood pressure, triglyceride concentrations, intraocular pressure, cylindrical refractive dioptre, presence of arteriolar sheathing, rural vsurban region, lower best-corrected visual acuity, lower high-density lipoprotein level, and lower diastolic blood pressure. It was not statistically associated with age, presence of cataract (nuclear, cortical, or subcapsular), size of the optic disc, neuroretinal rim, alphazone and betazone of peripapillary atrophy, retinal artery and vein diameters, arteriovenous nicking, focal or general narrowing, refractive error, prevalence of glaucoma, and early or late stage of age-related macular degeneration. In a population-based setting, diabetes mellitus was not associated with optic disc, rim and peripapillary atrophy measurements, retinal vessel diameters, arteriovenous nicking, focal or general retinal artery narrowing, and prevalence of age-related macular degeneration. Although diabetes mellitus was significantly correlated with higher intraocular pressure, it was not associated with glaucoma.

Long-standing, insulin-treated type 2 diabetes patients with complications respond well to short-term resistance and interval exercise training

To determine the feasibility and the benefits of combined resistance and interval exercise training on phenotype characteristics and skeletal muscle function in deconditioned, type 2 diabetes (T2D) patients with polyneuropathy. Short-term, single-arm intervention trial. Eleven male T2D patients (age: 59.1+/-7.5 years; body mass index: 32.2+/-4.0 kg/m2) performed progressive resistance and interval exercise training thrice a week for 10 weeks. Besides primary diabetes outcome measures, muscle strength (MUST), maximal workload capacity (Wmax), whole-body peak oxygen uptake (VO2peak) and muscle oxidative capacity (MUOX), intramyocellular lipid (IMCL) and glycogen (IMCG) storage, and systemic inflammation markers were determined before and after training. Daily exogenous insulin requirements (EIR) and historic individualized EIR were gathered and analysed. MUST and Wmax increased with 17% (90% confidence intervals 9-24%) and 14% (6-21) respectively. Furthermore, mean arterial blood pressure declined with 5.5 mmHg (-9.7 to -1.4). EIR dropped with 5.0 IU/d (-11.5 to 1.5) compared with baseline. A decline of respectively -0.7 mmol/l (-2.9 to 1.5) and -147 micromol/l (-296 to 2) in fasting plasma glucose and non-esterified fatty acids concentrations were observed following the intervention, but these were not accompanied by changes in VO2peak, MUOX, IMCL or IMCG, and blood glycolysated haemoglobin, adiponectin, tumor necrosis factor-alpha and/or cholesterol concentrations. Short-term resistance and interval exercise training is feasible in deconditioned T2D patients with polyneuropathy and accompanied by moderate improvements in muscle function and blood pressure. Such a specific exercise regimen may provide a better framework for future exercise intervention programmes in the treatment of deconditioned T2D patients.