Normal Fasting Glucose Levels Research Articles

Abstract WP167: Low Fasting Blood Glucose and Risks of Vascular and Mortality Outcomes in General Population: A Systematic Review and Meta-Analysis

Background and Purpose: Although low fasting blood glucose may imply poor nutrition status or hyperinsulinemia, whether low fasting blood glucose level increases future risks of stroke, cardiovascular disease, and mortality remain unsettled. We conducted a meta-analysis to examine the effect of low fasting blood glucose on subsequent major vascular outcomes in general populations without previous cardiovascular disease history. Methods: We searched PubMed and EMBASE from 1966 to June 2017. We included prospective cohort studies, which evaluated the effects of low and normal fasting glucose levels (4.7-5.5 mmol/L) on future risks of stroke, coronary heart disease, cardiovascular disease, and mortality. We analyzed data with cutoff levels of low fasting glucose level < 4.6 mmol/L and 4.0 mmol/L, respectively. Hazard ratio and 95 % confidence intervals were used to measure association between low fasting glucose levels and the risks of outcomes using random effect models. Results: We included 10 articles (consisting of 129 prospective cohort studies) that met our criteria; 3,277,497 participants were included in current meta-analysis. Comparing with the normal glucose group, low fasting blood glucose defined as < 4.6 mmol/L was not associated with the risk of stroke (adjusted HR 1.02, 0.99 to 1.06) or coronary heart disease (adjusted HR 1.02, 0.96 to 1.08), but was associated with an increased risk of all-cause mortality (adjusted HR 1.36, 1.06 to 1.75) (Fig 1 A), and total cardiovascular events (adjusted HR 1.03, 1.02 to 1.05). Using < 4.0 mmol/L as a cutoff level for low fasting blood glucose showed similar results (Fig 1B). Conclusions: Low fasting blood glucose is not associated with increased risk of stroke or coronary heart disease, but is associated with an increased all-cause mortality in the general population.

Predictors of Incident Type 2 Diabetes Mellitus in Japanese Americans with Normal Fasting Glucose Level.

BackgroundLittle is known about the natural course of normal fasting glucose (NFG) in Asians and the risk factors for future diabetes.MethodsA total of 370 Japanese Americans (163 men, 207 women) with NFG levels and no history of diabetes, aged 34 to 75 years, were enrolled. Oral glucose tolerance tests were performed at baseline, 2.5, 5, and 10 years after enrollment.ResultsDuring 10 years of follow-up, 16.1% of participants met criteria for diabetes diagnosis, and 39.6% of subjects still had NFG levels at the time of diabetes diagnosis. During 5 years of follow-up, age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01 to 1.10; P=0.026) and family history of diabetes (OR, 3.24; 95% CI, 1.42 to 7.40; P=0.005) were independently associated with future diabetes diagnosis; however, fasting glucose level was not an independent predictor. During 10 years of follow-up, family history of diabetes (OR, 2.76; 95% CI, 1.37 to 5.54; P=0.004), fasting insulin level (OR, 1.01; 95% CI, 1.00 to 1.02; P=0.037), and fasting glucose level (OR, 3.69; 95% CI, 1.13 to 12.01; P=0.030) were associated with diabetes diagnosis independent of conventional risk factors for diabetes.ConclusionA substantial number of subjects with NFG at baseline still remained in the NFG range at the time of diabetes diagnosis. A family history of diabetes and fasting insulin and glucose levels were associated with diabetes diagnosis during 10 years of follow-up; however, fasting glucose level was not associated with diabetes risk within the relatively short-term follow-up period of 5 years in subjects with NFG.

Could Insulin and Hemoglobin A1c Levels be Predictors of Hunger- Related Malnutrition/Undernutrition Without Disease?

Malnutrition results in functional changes in the liver and pancreas that negatively affect carbohydrate metabolism. The aim of this study was to evaluate whether insulin hormone and glycated hemoglobin A1c (HbA1c) could serve as predictors of hunger-related malnutrition/undernutrition without disease in adults. The Malnutrition Universal Screening Tool (MUST) was used to assess malnutrition in this single-center, cross-sectional study. The malnourished group (n = 67) comprised patients with a MUST score of ≥ 2, and the control group (n = 31) included subjects with a MUST score of 0 - 1. Serum albumin, prealbumin, C-reactive protein (CRP), fasting glucose, fasting insulin, hemoglobin and HbA1c levels, body mass index (BMI), and homoeostatic model for insulin resistance (HOMA-IR) scores were compared between the two groups. No significant difference was determined between the control and malnourished groups in respect of age or gender. HbA1c [5.5% (5 - 6.2) vs. 5.2% (3.9 - 6.7), p = 0.001], insulin levels [7.37 (2.36 - 52.16) vs. 3.91(1.17 - 30.08) µIU/mL, p < 0.001], and BMI [21.7 (14.1 - 34.0) vs. 17.8 (12.0 - 26.6) kg/m2, p < 0.001] were significantly lower in the malnourished group. Logistic regression analysis revealed that BMI was the only significant parameter (odds ratio [95% confidence interval] 0.680 [0.543 - 0.852]). Plasma insulin and HbA1c levels were significantly decreased in young adult malnourished patients without disease who had normal fasting glucose levels. These two parameters are known to be unaffected by inflammatory states, and therefore warrant further research on larger and different age sub-populations to assess if they might be early predictors of hunger-related malnutrition without disease.

Long-term feeding of high-fat plus high-fructose diet induces isolated impaired glucose tolerance and skeletal muscle insulin resistance in miniature pigs

BackgroundDuring the prediabetic development, the changes in β-cell function and tissue-specific insulin resistance have been described. However, there are conflicting views in insulin secretory capacity between early clinical observation and recent proposed mathematical model. On the basis of digestive and metabolic similarities with humans, swine have great potential as an animal model to investigate the progressive mechanisms of prediabetes. The aim of this study was to investigate the insulin secretory response and tissue-specific insulin resistance in a dietary-induced prediabetic porcine model.MethodsAdult male Taiwan Lee-Sung miniature pigs were randomized into two groups: (1) low-fat diet and (2) high-fat plus high-fructose diet (HFHF; 20.9% crude fat and 17.8% fructose). During the 12-month dietary intervention, body weights and blood glucose levels were measured monthly. Intravenous glucose tolerance test was used for measuring glucose tolerance and insulin secretory capacity. At the end of the experiment, liver and soleus muscle specimens were collected for ex vivo insulin sensitivity testing.ResultsThe results showed that the HFHF group had obesity, hyperinsulinemia, and dyslipidemia, but normal fasting glucose levels. The HFHF pigs exhibited enhanced first- and second-phase insulin secretion and high 2-h postload glucose levels in intravenous glucose tolerance test. Furthermore, the skeletal muscle specimens from the HFHF group were desensitized to insulin stimulation as shown by the lack of AKT Ser473 phosphorylation; however, the liver specimens remained a normal response.ConclusionsIn conclusion, the HFHF diet-fed pigs developed isolated impaired glucose tolerance corresponding to prediabetes with an intense insulin secretory response and skeletal muscle insulin resistance.

Blood Glucose Levels in Diabetic Patients Following Corticosteroid Injections into the Subacromial Space of the Shoulder.

Corticosteroid injections are used to treat a variety of orthopedic conditions with the goal of decreasing pain and inflammation. Administration of systemic or local corticosteroids risks temporarily increasing blood glucose levels, especially diabetic patients. The purpose of this study is to quantify the effects of corticosteroid injections on blood glucose levels in diabetic patients with shoulder pathology. Diabetic patients who regularly monitored their blood glucose levels and were indicated for a subacromial corticosteroid injection were included in this prospective investigation. The typical normal morning fasting glucose and most recent hemoglobin A1c level was recorded for each patient. After injection, patients were contacted daily to confirm their fasting morning glucose level for 10 days post-injection. Seventeen consecutive patients were enrolled. Patients with hemoglobin A1c of <7% had an average rise in blood glucose of 38 mg/dL compared to 98 mg/dL in the poorly controlled group after injection (P<0.001). Well-controlled patients' glucose levels returned to near baseline levels around post-injection day 8, while poorly controlled patients levels remained elevated. Similarly, insulin-dependent diabetic patients had an average increase in fasting glucose level of 99 mg/dL versus 50 mg/dL in non-insulin-dependent diabetic patients (P<0.001). After corticosteroid injection, patients with well-controlled diabetes experience smaller elevations and faster return to baseline glucose levels than patients with poor control. Insulin dependent diabetics experienced similar findings as patients with poor control. Future studies are needed to evaluate dosing to optimize the risks of blood glucose elevation while maintaining therapeutic benefit.

Use of HOMA-IR to diagnose non-alcoholic fatty liver disease: a population-based and inter-laboratory study.

Recent European guidelines for non-alcoholic fatty liver disease (NAFLD) call for reference values for HOMA-IR. In this study, we aimed to determine: (1) the upper limit of normal HOMA-IR in two population-based cohorts; (2) the HOMA-IR corresponding to NAFLD; (3) the effect of sex and PNPLA3 genotype at rs738409 on HOMA-IR; and (4) inter-laboratory variations in HOMA-IR. We identified healthy individuals in two population-based cohorts (FINRISK 2007 [n=5024] and the Programme for Prevention of Type 2 Diabetes in Finland [FIN-D2D; n=2849]) to define the upper 95th percentile of HOMA-IR. Non-obese individuals with normal fasting glucose levels, no excessive alcohol use, no known diseases and no use of any drugs were considered healthy. The optimal HOMA-IR cut-off for NAFLD (liver fat ≥5.56%, based on the Dallas Heart Study) was determined in 368 non-diabetic individuals (35% with NAFLD), whose liver fat was measured using proton magnetic resonance spectroscopy (1H-MRS). Samples from ten individuals were simultaneously analysed for HOMA-IR in seven European laboratories. The upper 95th percentiles of HOMA-IR were 1.9 and 2.0 in healthy individuals in the FINRISK (n=1167) and FIN-D2D (n=459) cohorts. Sex or PNPLA3 genotype did not influence these values. The optimal HOMA-IR cut-off for NAFLD was 1.9 (sensitivity 87%, specificity 79%). A HOMA-IR of 2.0 corresponded to normal liver fat (<5.56% on 1H-MRS) in linear regression analysis. The 2.0 HOMA-IR measured in Helsinki corresponded to 1.3, 1.6, 1.8, 1.8, 2.0 and 2.1 in six other laboratories. The inter-laboratory CV% of HOMA-IR was 25% due to inter-assay variation in insulin (25%) rather than glucose (5%) measurements. The upper limit of HOMA-IR in population-based cohorts closely corresponds to that of normal liver fat. Standardisation of insulin assays would be the first step towards definition of normal values for HOMA-IR.

Metabolic syndrome components and diabetes incidence according to the presence or absence of impaired fasting glucose: The Japan Epidemiology Collaboration on Occupational Health Study.

BackgroundWe prospectively examined the association of diabetes risk with the number of metabolic abnormalities, as well as their combinations, according to the presence or absence of impaired fasting glucose (IFG) in a large-scale Japanese working population.MethodsParticipants included 55,271 workers at 11 companies who received periodic health check-ups between 2008 and 2013. The metabolic syndrome (MetS) components were defined using the 2009 Joint Interim Statement. IFG was defined as fasting plasma glucose 5.6–6.9 mmol/L. Diabetes newly diagnosed after the baseline examination was defined according to the American Diabetes Association criteria. We calculated the hazard ratios (HRs) for diabetes incidence using the Cox proportional hazards model.ResultsDuring the follow-up period (median 4.95 years), 3183 subjects developed diabetes. In individuals with normal fasting glucose levels, the risk of diabetes increased steadily with the increasing number of MetS components; the multivariable-adjusted HRs for incident diabetes for the number of MetS components were 2.0, 4.3, 7.0, and 10.0 for one, two, three, or four MetS components, respectively, compared with the absence of components. A similar association was observed among individuals with IFG; the corresponding HRs were 17.6, 23.8, 33.9, and 40.7. The combinations that included central obesity appeared to be more strongly associated with diabetes risk than other combinations with the same number of MetS components within the same glucose status.ConclusionsOur findings indicate that risk stratification of individuals by the presence or absence of IFG and the number of MetS components can detect individuals with a high risk of diabetes.

Higher Fasting Plasma Glucose is Associated with Increased Cortical Thinning Over 12 Years: The PATH Through Life Study.

Recent evidence suggests that type 2 diabetes (T2D) is associated with accelerated brain ageing, consistent with the observation of increased risk of cognitive impairment and dementia in affected individuals. Even non-diabetic individuals with impaired fasting plasma glucose (IFG) levels have shown increased cerebral atrophy, compared to individuals with normal glucose levels. We tested whether longitudinal rates of age-related cortical thinning were associated with fasting plasma glucose levels in a large sample (n = 322) of early-old age individuals (60-66 years) who were scanned with magnetic resonance imaging (1.5T) on up to four occasions over 12 years. Higher plasma glucose levels (measured on up to three occasions) were associated with increased cortical thinning in individuals with T2D as well as those with IFG, with a similar trend for individuals with normal fasting glucose (NFG) levels. Across groups, a 1mmol/l increase in plasma glucose (above 5mmol/l in NFG and IFG and above 6.1mmol/l in T2D) resulted in a 10-13% increase in annual cortical thinning. Increased cortical thinning was detected in insular cortex, as well as posterior cingulate, parahippocampus and medial orbitofrontal cortex. Our results provide support for the idea that raised plasma glucose levels, even in the normal range, are associated with accelerated age-related cortical atrophy.

Diabetes Mellitus in Thalassaemia Major Patients: A Report from the Southeast of Iran.

Diabetes Mellitus (DM) represents a major concern in Thalassaemia Major (TM) patients. The present study was conducted to evaluate the frequency of Impaired Fasting Glucose (IFG) and DM in TM patients in Southeast of Iran. Fasting Blood Glucose (FBS) was determined using fasting blood samples in 148 TM patients. Demographical data was collected by a questionnaire. Clinical and laboratory variables including cell blood counts, pre-transfusion Haemoglobin (Hb) level, and five-year ferritin were extracted from medical records. Statistical analysis was performed in SPSS19.0 software using chi-square, student t-test and logistic regression. Females and males comprised 83 (56.1%) and 65 (43.9%) subjects respectively. The mean age and mean five-year ferritin were 17.3±6.1 year-old and 5060.6±2395 ng/ml respectively. Overall, 39 (26.4%) patients had IFG, while 13 (8.8%) were diagnosed with DM. Significant differences were identified in the mean age, volume of transfused blood per occasion, and mean five-years ferritin between the patients with IFG or DM and the patients with normal fasting glucose level. Patients with age >25-year-old had an increased risk of both IFG (OR=4.7,95% CI: 1.3-17, p=0.01) and DM (OR= 7.1, 95% CI: 1-49.2, p=0.04). In addition, splenectomized patients showed a higher risk for IFG (OR=4.3, 95% CI: 1.5-12.1, p=0.005), and ferritin value >6000 ng/ml were associated with an elevated risk of DM (OR=7, 95% CI: 0.8-60.1, p=0.07). Our results indicated that higher age, mean five-years ferritin, volume of blood transfused per occasion, as well as splenectomy were risk factors of IFG and DM in TM patients.

Hepatogenous diabetes: Is it time to separate it from type 2 diabetes?

By definition, hepatogenous diabetes is directly caused by loss of liver function, implying that it develops after cirrhosis onset. Therefore, it should be distinguished from type 2 diabetes developing before cirrhosis onset, in which specific causes of liver disease play a major role, in addition to traditional risk factors. Currently, although hepatogenous diabetes shows distinct pathophysiological and clinical features, it is not considered as an autonomous entity. Recent evidence suggests that the failing liver exerts an independent "toxic" effect on pancreatic islets resulting in β-cell dysfunction. Moreover, patients with hepatogenous diabetes usually present with normal fasting glucose and haemoglobin A1c levels and abnormal response to an oral glucose tolerance test, which is therefore required for diagnosis. This article discusses the need to separate hepatogenous diabetes from type 2 diabetes occurring in subjects with chronic liver disease and to identify individuals suffering from this condition for prognostic and therapeutic purposes.

Factor XIII-A transglutaminase deficient mice show signs of metabolically healthy obesity on high fat diet

F13A1 gene, which encodes for Factor XIII-A blood clotting factor and a transglutaminase enzyme, was recently identified as a potential causative gene for obesity in humans. In our previous in vitro work, we showed that FXIII-A regulates preadipocyte differentiation and modulates insulin signaling via promoting plasma fibronectin assembly into the extracellular matrix. To understand the role of FXIII-A in whole body energy metabolism, here we have characterized the metabolic phenotype of F13a1−/− mice. F13a1−/− and F13a1+/+ type mice were fed chow or obesogenic, high fat diet for 20 weeks. Weight gain, total fat mass and fat pad mass, glucose handling, insulin sensitivity, energy expenditure and, morphological and biochemical analysis of adipose tissue was performed. We show that mice lacking FXIII-A gain weight on obesogenic diet, similarly as wild type mice, but exhibit a number of features of metabolically healthy obesity such as protection from developing diet-induced insulin resistance and hyperinsulinemia. Mice also show normal fasting glucose levels, larger adipocytes, decreased extracellular matrix accumulation and inflammation of adipose tissue, as well as decreased circulating triglycerides. This study reveals that FXIII-A transglutaminase can regulate whole body insulin sensitivity and may have a role in the development of diet-induced metabolic disturbances.

The association between maternal hyperglycemia and perinatal outcomes in gestational diabetes mellitus patients: A retrospective cohort study.

Pregnancies complicated by gestational diabetes mellitus (GDM) are associated with increased risks of adverse maternal and fetal outcomes. The risks of adverse pregnancy outcomes differ depending on the glucose values among GDM patients. For accurate and effective prenatal counseling, it is necessary to understand the relationship between different maternal hyperglycemia values and the severity of adverse outcomes. With this objective, this study reexamines the relationship between maternal hyperglycemia versus maternal and perinatal outcomes in GDM patients. For this study, maternal hyperglycemia was diagnosed using the 2-step diagnostic approach.Medical records of 3434 pregnant women, who received the 50-g glucose challenge test (GCT) between March 2001 and April 2013, were reviewed. As a result, 307 patients were diagnosed with GDM, and they were divided into 2 groups according to their fasting glucose levels. A total of 171 patients had normal fasting glucose level (<95 mg/dL), and 136 patients had abnormal fasting glucose level (≥95 mg/dL). The 50-g GCT results were subdivided by 20-unit increments (140–159, n = 123; 160–179, n = 84; 180–199, n = 50; and ≥200, n = 50), and the maternal and perinatal outcomes were compared against the normal 50-g GCT group (n = 307).Maternal fasting blood glucose (FBG) level showed clear association with adverse perinatal outcomes. The odds ratio (OR) of macrosomia was 6.72 (95% CI: 2.59–17.49, P < 0.001) between the 2 groups. The ORs of large for gestational age (LGA) and neonatal hypoglycemia were 3.75 (95% CI: 1.97–7.12, P < 0.001) and 1.65 (95% CI: 0.79–3.43, P = 0.183), respectively. Also, the results of the 50-g GCT for each category showed strong association with increased risks of adverse perinatal outcomes compared to the normal 50-g GCT group. The OR of macrosomia (up to 20.31-fold), LGA (up to 6.15-fold), and neonatal hypoglycemia (up to 84.00-fold) increased with increasing 50-g GCT result.

A Variant in ADIPOR2 Is Associated with Increased Free Fatty Acid Levels in Chinese Population.

Elevated free fatty acids (FFAs) are thought to play an important role in the development of insulin resistance. Adiponectin is an adipose tissue-secreted protein known for its effects on the stimulation of fatty acid oxidation. The aim of this study was to investigate the association of adiponectin receptor 2 gene variations with FFAs levels in subjects with normal fasting glucose levels in Chinese Han population. Four common single nucleotide polymorphisms of ADIPOR2 were genotyped using the TaqMan method to perform association studies with metabolic parameters in 1819 subjects among Chinese Han population. All the subjects were divided into two groups: normal FFAs group (FFAs ≤0.88 mmol/L) and high FFAs group (FFAs >0.88 mmol/L). There was a significant association of rs2370055 with higher FFA levels in major T-allele carriers (P = 0.000). There was a significant difference in the distribution of genotypes of polymorphism rs2370055 between normal and high FFA groups. The frequencies of TT and CT genotypes are significantly higher in subjects with high FFA level than those in the normal FFAs group (P = 0.013 and P = 0.004, respectively). After adjustment for age, sex, body mass index, triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoproteincholesterol, the TT and CT genotypes are both independent risk factors for high FFAs level. Our findings suggest that variants of ADIPOR2 could be a determinant for higher FFA levels, and among Chinese Han population, carriers of the CT and TT genotypes for rs2370055 even with normal glucose levels may have significantly higher insulin resistance susceptibility.

Impaired insulin action in the liver, but not in adipose tissue or muscle, is a distinct metabolic feature of impaired fasting glucose in obese humans

AimElevated basal endogenous glucose production (EGP), impaired suppression of EGP by insulin and reduced insulin-stimulated glucose disposal are cornerstones of the pathogenesis of hyperglycemia in patients with type 2 diabetes. We aimed to determine the contribution of these processes to impaired fasting glucose (IFG) levels in obese non-diabetic adults. MethodsWe included 131 obese non-diabetic adults with normal fasting glucose levels (NFG; fasting glucose <5.6mmol/L; 62 men, 25 women; mean±SEM age 49±1years; median (IQR) BMI 36 (34–41) kg/m2) or IFG (fasting glucose 5.6–6.9mmol/L; 35 men, 9 women; age 53±1years; BMI 36 (34–42) kg/m2) and studied basal EGP and hepatic, adipose tissue and peripheral insulin sensitivity by two-step euglycemic hyperinsulinemic clamp studies with [6,6-2H2]glucose infusion. ResultsCompared to equally obese adults with NFG, individuals with IFG did not differ in basal EGP (9.1±0.2 vs 9.8±0.3μmolkg−1min−1, p=0.082), insulin-mediated suppression of circulating free fatty acid levels (75±1 vs 72±3%, p=0.240) and insulin-stimulated glucose disposal (26.6±1.0 vs 25.2±1.5μmolkg−1min−1, p=0.441). Insulin-mediated suppression of EGP (68±2 vs 55±3%, p<0.001) was markedly reduced in obese subjects with IFG. ConclusionsHepatic insulin resistance is a distinct metabolic feature of IFG in obesity. Insulin sensitivity of free fatty acid suppression and skeletal muscle does not differ between obese people with NFG and IFG. Hepatic insulin resistance may contribute to the onset of prediabetes in obese adults.

Exercise Heart Rate Reserve and Recovery as Predictors of Incident Type 2 Diabetes

BackgroundWe tested the hypothesis that selected exercise heart rate responses, specifically those providing indices of autonomic dysfunction, may be associated with incident type 2 diabetes in 2231 apparently healthy men with normal baseline fasting glucose levels. MethodsHeart rate reserve was calculated as the difference between the maximal attained heart rate and the supine resting heart rate, whereas heart rate recovery was defined as the maximal heart rate minus the heart rate measured at 2 minutes of recovery after peak or symptom-limited cardiopulmonary exercise testing. Type 2 diabetes was defined as glycated hemoglobin >6.5% or fasting plasma glucose >126 mg/dL at the follow-up examination. ResultsDuring a median follow-up interval of 5 years, 90 of the 2231 men (4.0%) developed type 2 diabetes. The relative risks of incident type 2 diabetes in men within the lowest quartiles of heart rate reserve and heart rate recovery versus men comprising the highest quartiles of heart rate reserve and heart rate recovery were 2.71 (95% confidence interval, 1.20-6.11) and 2.81 (95% confidence interval, 1.36-5.78) after adjusting for potential confounding variables. Each unit increment (1 beat/min) in heart rate reserve and heart rate recovery was associated with a 2% to 3% decreased incidence of type 2 diabetes. ConclusionsExercise heart rate reserve and recovery predicted incidence of type 2 diabetes in healthy men, suggesting that autonomic dysfunction may be associated with an increased likelihood for the development of this cardiometabolic risk factor.

Exenatide Is an Effective Antihyperglycaemic Agent in a Mouse Model of Wolfram Syndrome 1.

Wolfram syndrome 1 is a very rare monogenic disease resulting in a complex of disorders including diabetes mellitus. Up to now, insulin has been used to treat these patients. Some of the monogenic forms of diabetes respond preferentially to sulphonylurea preparations. The aim of the current study was to elucidate whether exenatide, a GLP-1 receptor agonist, and glipizide, a sulphonylurea, are effective in a mouse model of Wolfram syndrome 1. Wolframin-deficient mice were used to test the effect of insulin secretagogues. Wolframin-deficient mice had nearly normal fasting glucose levels but developed hyperglycaemia after glucose challenge. Exenatide in a dose of 10 μg/kg lowered the blood glucose level in both wild-type and wolframin-deficient mice when administered during a nonfasted state and during the intraperitoneal glucose tolerance test. Glipizide (0.6 or 2 mg/kg) was not able to reduce the glucose level in wolframin-deficient animals. In contrast to other groups, wolframin-deficient mice had a lower insulin-to-glucose ratio during the intraperitoneal glucose tolerance test, indicating impaired insulin secretion. Exenatide increased the insulin-to-glucose ratio irrespective of genotype, demonstrating the ability to correct the impaired insulin secretion caused by wolframin deficiency. We conclude that GLP-1 agonists may have potential in the treatment of Wolfram syndrome-related diabetes.

Comparison between the Oral Glucose Tolerance Test and the Hba1c Assay for Detecting Impaired Glucose Regulation in Bahamian Adolescents

Objective: To determine the best method for detecting Impaired Glucose Regulation (IGR) in adolescents from New Providence Island, Bahamas. IGR is defined by blood glucose levels that are higher than normal but below those of a person with diabetes. Design and Methods: From Jan-March 2012, 873 adolescents (13-19 years old) were randomly selected from five different high schools in New Providence. Weight and height were measured and participants were screened for IGR using the hemoglobin A1c (HbA1c) test and a 2-hour oral glucose tolerance test (OGTT). T-test or chi-square test was used to determine significant associations between sex and outcome variables, and prevalence of glycemic status by BMI category. Linear regression was used to determine the relationship between OGTT results and BMI. Results: Of the initial pool, 861 adolescents (98.6%) completed the study. The OGTT demonstrated that 89.4% of these students had normal fasting glucose levels and 98.8% had normal 2-hour OGTT glucose levels. Eightyseven students (37 boys and 50 girls) had elevated fasting plasma glucose; however, 2 hours after the oral glucose load, only 9 students (2 boys and 7 girls) had blood glucose concentrations indicative of IGR. For the HbA1c test, 82.6% of the students had normal results, and 1.3% had diabetes. The HbA1c test revealed a higher percentage of students with IGR (16.1%) than the OGTT (1%). Conclusions: The HbA1c test identified a greater percentage of adolescents as having IGR than did the OGTT. Due to the high discordance between the two tests, it is likely that an elevated HbA1c test may falsely classify adolescents as IGR if OGTT results and clinical signs (e.g., diabetic retinopathy and/or nephropathy) are not considered.

Usefulness of pulse wave velocity as an indicator of atherosclerosis in subjects with impaired fasting glucose

Background: The prediabetic state with impaired fasting glucose level (IFG) is one of the risk factors for endothelial dysfunction leading to atherosclerosis. Pulse wave velocity is an effective index of arterial stiffness and is widely used for noninvasive assessment of atherosclerosis. Aims and Objectives: To assess the usefulness of pulse wave velocity (PWV) as an indicator of atherosclerosis in IFG. Also to compare PWV values in subjects with IFG and those with normal fasting glucose (NFG) levels and to correlate the PWV values with the fasting glucose levels. Materials and Methods: Two hundred male subjects were involved in the study. Group 1 comprised subjects with IFG (n = 100). Group 2 comprised subjects with NFG (n = 100). Both the groups were evaluated for physiological parameters-Blood pressure and brachial-ankle pulse wave velocity (ba-PWV) using PeriScope. The biochemical parameters such as fasting blood glucose, HbA1c, and lipid profile were also measured. Statistical analysis was done using SPSS-19 software. All parameters were compared using unpaired Student’s t-test. Pearson correlation analysis was done to establish the relationship between two variables. Results: Significant differences were found between the ba-PWV values in the IFG and NFG groups (1549.5 ± 60.5 cm/s vs 1351.7 ± 44.0 cm/s, p < 0.05). There was also significant positive correlation (r = 0.88) between ba-PWV value and fasting glucose level. The multiple regression analysis showed that IFG level is an independent risk factor for increased ba-PWV levels. Conclusion: Our study showed that ba-PWV can be used as an indicator to detect the early development of atherosclerosis in subjects with IFG levels.

Chewing the fat for better insulin secretion.

Chewing the fat for better insulin secretion.

Performance of HbA1c for the prediction of diabetes in a rural community in Korea.

To investigate the performance of HbA1c in predicting incident diabetes among Korean adults with normal fasting glucose and impaired fasting glucose levels. This study used data from the Korean Genome Epidemiology Study-Kangwha Study. A prospective analysis was carried out on 2079 people (820 men and 1259 women) who completed follow-up examinations up until 2013. Diabetes was defined as fasting blood glucose level ≥ 7.0 mmol/l, HbA1c level ≥ 48 mmol/mol (6.5%), or current treatment for diabetes. Areas under the receiver-operating characteristic curves were used to assess the different performances of HbA1c , glucose and insulin in predicting diabetes. The median follow-up time was 3.97 years, during which 7.7% of men and 6.3% of women developed incident diabetes. The areas under the receiver-operating curves (95% CI) for diabetes prediction were 0.740 (0.692-0.787) for HbA1c , 0.716 (0.667-0.764) for glucose and 0.598 (0.549-0.648) for insulin. HbA1c showed better predictive power in people with impaired fasting glucose (area under the curve 0.753, 95% CI 0.685-0.821) than in those with normal glucose (area under the curve 0.648, 95% CI 0.577-0.719). An HbA1c threshold of 40 mmol/mol (5.8%) was found to have the highest predictive value for diabetes, with a relative risk of 6.30 (95% CI 3.49-11.35) in men and 3.52 (95% CI 2.06-6.03) in women after adjusting for age, waist circumference, triglycerides, hypertension, family history of diabetes, smoking, alcohol intake, exercise and baseline glucose level. HbA1c can be used to identify people at high risk for the development of diabetes, especially in those with impaired fasting glucose levels.