Heterogeneity of pregnancy outcomes and risk of LGA neonates in Caucasian females according to IADPSG criteria for gestational diabetes mellitus

ObjectiveThe International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines for gestational diabetes mellitus (GDM) diagnosis determines that fasting, 1-h and 2-h glucose values may contribute independently to adverse outcomes. However, given the different physiological bases of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), differences in pregnancy outcomes are to be expected. This study aimed to determine whether classification of GDM women according to glucose homoeostasis results in heterogeneity in maternal and/or fetal outcomes.Material and methodsOf the 75 pregnant women included after a 75-g 2-h OGTT performed between weeks 24–32 of gestation as per WHO criteria, 55 were classified as GDM (16 with IFG and 39 with IGT) according to IADSPG criteria. Their anthropometric and metabolic characteristics were compared with those of non-GDM women with IFG or IGT. Maternal and neonatal outcomes were prospectively recorded for each group.ResultsGDM women with IFG, including isolated IFG and combined IFG + IGT, were significantly heavier, had higher leptin values and were more frequently multiparous than GDM women with isolated IGT. HOMA-IR was significantly higher when fasting glucose was impaired. There were no significant differences in maternal outcomes according to metabolic status. In addition, large for gestational age (LGA) neonates were significantly seen more often in the IFG group. Fasting glucose was significantly associated with LGA independently of BMI and 2-h OGTT glucose. The > 5.1 mmol/L cut-off value for fasting glucose was highly predictive of delivery of LGA infants.ConclusionIFG in GDM women was associated with increases in BMI, fat mass and hepatic insulin resistance. Delivery of LGA neonates was more frequent when fasting glycaemia was increased during the third trimester of pregnancy, and was independent of BMI and 2-h OGTT glucose values.     

Shape of the OGTT glucose curve and risk of impaired glucose metabolism in the EGIR-RISC cohort

ObjectiveTo study whether the shape of the oral glucose tolerance test (OGTT)-glucose curve is a stable trait over time; it is associated with differences in insulin sensitivity, ß-cell function and risk of impaired fasting glucose (IFG) and glucose tolerance (IGT) in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort.MethodsOGTT-glucose curve shape was classified as monophasic, biphasic, triphasic and anomalous in 915 individuals. Oral glucose insulin sensitivity (OGIS), Matsuda insulin sensitivity index (ISI) and ß-cell function were assessed at baseline and 3 years apart.ResultsThe OGTT-glucose curve had the same baseline shape after 3 years in 540 people (59%; κ = 0.115; p < 0.0001). Seventy percent of the participants presented with monophasic OGTT-glucose curve shape at baseline and after 3 years (percent positive agreement 0.74). Baseline monophasic shape was associated with significant increased risk of IFG (OR 1.514; 95% CI 1.084–2.116; p = 0.015); biphasic shape with reduced risk of IGT (OR 0.539; 95% CI 0.310–0.936) and triphasic shape with reduced risk of IFG (OR 0.493; 95% CI 0.228–1.066; P = 0.043) after 3 years. Increased risks of IFG (OR 1.509; 95% CI 1.008–2.260; p = 0.05) and IGT (OR 1.947; 95% CI 1.085–3.494; p = 0.02) were found in people who kept stable monophasic morphology over time and in switchers from biphasic to monophasic shape (OR of IGT = 3.085; 95% CI 1.377–6.912; p = 0.001).ConclusionAfter 3 years follow-up, the OGTT-glucose shape was stable in 59% of the RISC cohort. Shapes were associated with different OGIS and ß-cell function; persistence over time of the monophasic shape and switch from biphasic to monophasic shape with increased risk of impaired glucose metabolism.     

The relative associations of β-cell function and insulin sensitivity with glycemic status and incident glycemic progression in migrant Asian Indians in the United States: The MASALA study

AimsWe assessed the relative associations of β-cell dysfunction and insulin sensitivity with baseline glycemic status and incident glycemic progression among Asian Indians in the United States.MethodsA 5-sample oral glucose tolerance test was obtained at baseline. Normoglycemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM) were defined by ADA criteria. The Matsuda Index (ISI_M) estimated insulin sensitivity, and the Disposition Index (DI_o) estimated β-cell function. Visceral fat was measured by abdominal CT. After 2.5 years, participants underwent a 2-sample oral glucose tolerance test. Standardized polytomous logistic regression was used to examine associations with prevalent and incident glycemia.ResultsMean age was 57 ± 8 years and BMI 26.1 ± 4.6 kg/m². Log ISI_M and log DI_o were associated with prediabetes and T2DM after adjusting for age, sex, BMI, family history of diabetes, hypertension, and smoking. After adjusting for visceral fat, only DI_o remained associated with prediabetes (OR per SD 0.17, 95% CI: 0.70, 0.41) and T2DM (OR 0.003, 95% CI: 0.0001, 0.03). Incidence rates (per 1,000 person-years) were: normoglycemia to IGT: 82.0, 95% CI (40, 150); to IFG: 8.4, 95% CI (0, 41); to T2DM: 8.6, 95% CI (0, 42); IGT to T2DM: 55.0, 95% CI (17, 132); IFG to T2DM: 64.0, 95% CI (3, 316). The interaction between sex and the change in waist circumference (OR 1.8, per SD 95% CI: 1.22, 2.70) and the change in log HOMA-β (OR 0.37, per SD 95% CI: 0.17, 0.81) were associated with glycemic progression.ConclusionsThe association of DI_o with baseline glycemia after accounting for visceral fat as well as the association of the change in log HOMA-β with incident glycemic progression implies innate β-cell susceptibility in Asian Indians for glucose intolerance or dysglycemia.     

External validation of the Finnish diabetes risk score in Venezuela using a national sample: The EVESCAM

AimsTo evaluate the performance of the Latin American Finnish Diabetes Risk Score (LA-FINDRISC) compared with the original O-FINDRISC in general population. To establish the best cut-off to detect unknown type 2 diabetes (uT2D) and prediabetes.MethodsThe EVESCAM was a national population-based, cross-sectional, randomized cluster sampling study, which assessed 3454 adults from July 2014 to January 2017. Those with self-report of diabetes were excluded; a total of 3061 subjects were analyzed. Waist circumference adapted for Latin America was the difference between the LA-FINDRISC and the O-FINDRISC. The area under the curve (AUC), sensitivity, and specificity were calculated.ResultsThe prevalence of uT2D and prediabetes were 3.3% and 38.5%. The AUC with the LA-FINDRISC vs. the O-FINDRISC were: for uT2D, 0.722 vs. 0.729 in men (p = 0.854) and 0.724 vs. 0.732 in women (p = 0.896); for prediabetes (impaired fasting glucose [IFG] + impaired glucose tolerance [IGT], 0.590 vs. 0.587 in men (p = 0.887) and 0.621 vs. 0.627 in women (p = 0.777); for IFG, 0.582 vs. 0.580 in men (p = 0.924) and 0.607 vs. 0.617 in women (p = 0.690); for IGT, 0.691 vs. 0.692 in men (p = 0.971) and 0.672 vs. 0.671 in women (p = 0.974). Using the LA-FINDRISC, the best cut-offs to detect uT2D were 9 in men and 10 in women and to detect IGT was 9 in both genders.ConclusionLA-FINDRISC has similar performance than O-FINDRISC in Venezuelan adults and showed a good performance to detect uT2D and IGT, but not IFG. The best cut-offs to detect glucose alterations were established.     

Hypertriglyceridemia is associated with development of metabolic glucose disorders,irrespective of glucose and insulin levels: A 15-year follow-up study

BackgroundBecause the role of 2-h postload glucose and insulin levels as confounders in the relationship between hypertriglyceridemia and development of metabolic glucose disorders (MGD) has not been elucidated, the aim of this study was to determine whether triglyceride levels ≥ 1.7 mmol/L are a risk factor of developing MGD in otherwise healthy men and women.MethodsA total of 341 healthy men and non-pregnant women, 30 to 50 years of age, were enrolled in a 15-year follow-up study and allocated into the exposed (triglycerides ≥ 1.7 mmol/L) and non-exposed (triglycerides < 1.7 mmol/L) groups. Follow-up visits were scheduled every 3 years to complete 5 visits (mean 3.8 visits). At final follow-up, about 15 years later (mean 13.6 years), contact was re-established in 236 individuals to complete 3540 person-years of follow-up. At baseline, all subjects in both groups were required to be free of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG + IGT, and type 2 diabetes.ResultsThe Poisson regression models, adjusted by age, sex, family history of diabetes, waist circumference, body mass index, total body fat, blood pressure, fasting and postload glucose, fasting and postload insulin, and HOMA-IR index, showed a significant association between triglycerides ≥ 1.7 mmol/L and IFG (relative risk – RR – 1.40; 95% CI 1.2–2.2), IGT (RR 1.60; 95% CI 1.3–2.2), IFG + IGT (RR 1.80; 95% CI 1.5–2.7), and type 2 diabetes (RR 3.0; 95% CI 2.5–3.8).ConclusionsSerum triglyceride levels ≥ 1.7 mmol/L are an independent risk factor of developing IFG, IGT, IFG + IGT, and type 2 diabetes in young and middle-aged, men and women.     

Impaired early- but not late-phase insulin secretion in subjects with impaired fasting glucose

Subjects with impaired fasting glucose (IFG) are at increased risk for type 2 diabetes. We recently demonstrated that IFG subjects have increased hepatic insulin resistance with normal insulin sensitivity in skeletal muscle. In this study, we quantitated the insulin secretion rate from deconvolution analysis of the plasma C-peptide concentration during an oral glucose tolerance test (OGTT) and compared the results in IFG subjects with those in subjects with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). One hundred and one NGT subjects, 64 subjects with isolated IGT, 24 subjects with isolated IFG, and 48 subjects with combined (IFG + IGT) glucose intolerance (CGI) received an OGTT. Plasma glucose, insulin, and C-peptide concentrations were measured before and every 15 min after glucose ingestion. Insulin secretion rate (ISR) was determined by deconvolution of plasma C-peptide concentration. Inverse of the Matsuda index of whole body insulin sensitivity was used as a measure of insulin resistance; 56 subjects also received a euglycemic hyperinsulinemic clamp. The insulin secretion/insulin resistance (disposition) index was calculated as the ratio between incremental area under the ISR curve (∆ISR[AUC]) to incremental area under the glucose curve (∆G[AUC]) factored by the severity of insulin resistance (measured by Matsuda index during OGTT or glucose disposal during insulin clamp). Compared to NGT, the insulin secretion/insulin resistance index during first 30 min of OGTT was reduced by 47, 49, and 74% in IFG, IGT, and CGI, respectively (all < 0.0001). The insulin secretion/insulin resistance index during the second hour (60–120 min) of the OGTT in subjects with IFG was similar to that in NGT (0.79 ± 0.6 vs. 0.72 ± 0.5, respectively, P = NS), but was profoundly reduced in subjects with IGT and CGI (0.31 ± 0.2 and 0.19 ± 0.11, respectively; P < 0.0001 vs. both NGT and IFG). Early-phase insulin secretion is impaired in both IFG and IGT, while the late-phase insulin secretion is impaired only in subjects with IGT.     

Assessment of small fiber neuropathy to predict future risk of type 2 diabetes

ObjectiveSudomotor dysfunction due to small fiber neuropathy can be observed very early in pre-diabetes. The aim of this study was to assess the predictive power of EZSCAN, a non invasive, quick and simple measurement of sudomotor function to identify glucose impairment.Research design and methodsThe study was performed in 76 German subjects at risk of diabetes. Glucose metabolism was assessed by using, oral glucose tolerance test (OGTT) at baseline and after 2 year follow-up. Sudomotor function was evaluated by measuring hand and foot electrochemical sweat conductances to calculate a risk score.ResultsAt baseline, 38 patients had normal glucose tolerance (NGT), 34 had pre-diabetes (impaired fasting glucose, IFG and/or impaired glucose tolerance, IGT) and 4 had newly diagnosed type 2 diabetes. The AUC values for FPG, 2 h-OGTT glucose, 1 h-OGTT glucose, HbA_1C and EZSCAN score to predict pre-diabetes were 0.50, 0.65, 0.64, 0.72 and 0.76, respectively. Subjects having a moderate or high EZSCAN score (>50) at baseline had a substantially increased risk for having IFG and/or IGT at follow-up visit presented by an odds ratio of 12.0 [1.4–100.5], the OR for having 1 h-OGTT ≥ 8.6 mmol/L at follow-up was 9.8 [1.0–92.8] and for having HbA_1C ≥ 5.7% was 15.7 [1.9–131.5] compared to subjects with low EZSCAN risk.ConclusionsThis preliminary study, which must be confirmed in a larger population, shows that EZSCAN risk score is associated with diabetes progression which have implications for prevention and disease management.     

Elevated level of C-reactive protein is associated with risk of prediabetes in Indians

BackgroundRelationship of high sensitivity C-reactive protein (hsCRP) with prediabetes has not been explored extensively in Indians. Here we sought to investigate the association of hsCRP levels with prediabetes, as represented by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and the influence of risk factors like obesity, decreased HDL cholesterol, hypertension, family history of diabetes and current smoking habit on the relationship.MethodsA cross-sectional study on 1726 Indians, comprising of 1276 individuals with normal glucose tolerance (NGT), 250 IFG and 200 IGT individuals. Subjects were defined according to WHO criteria based on fasting plasma and 2 h glucose levels.ResultsMedian levels of hsCRP were significantly higher in IFG (2.20 mg/l) and IGT (2.32 mg/l) compared to NGT (1.64 mg/l) subjects. Individuals with high risk hsCRP levels (>3 mg/l) had an odds ratio (OR) (95% confidence interval (CI)) of 2.60 (1.56–5.34) [P = 1.3 × 10^?4] for IGT after adjusting the effect of age, sex, medication, body mass index (BMI), waist circumference (WC) and risk factors like decreased high-density lipoprotein cholesterol (HDL-cholesterol), hypertension, family history of diabetes and current smoking. Significant increase in risk of IGT was found with a unit increase in natural log transformed hsCRP levels after adjustment for covariates [OR (95%CI) = 1.57 (1.27–1.94), P = 3.0 × 10^?5]. When subjects were stratified on the basis of risk factors, we found stronger association of elevated hsCRP levels with risk of IFG and IGT in subjects having HDL-cholesterol ≤50 mg/dl and with hypertension.ConclusionsOur study demonstrates that elevated hsCRP levels are independently associated with risk of IFG and IGT in Indians.     

Metabolic syndrome of prediabetic and diabetic subjects in a Bangladeshi population

BackgroundThe metabolic syndrome is a cluster of medical disorder that increases the risk of developing cardiovascular disease and diabetes.Aims and objectiveObjective of the study was to determine the metabolic syndrome in prediabetic subjects to know whether this syndrome, which is common in diabetic subjects, appears in earlier stage of the disease.Materials and methodsA group of 17 IFG, 60 IGT, 29 combined IFG–IGT and 68 type 2 DM subjects were studied along with a group of 56 healthy controls. Anthropometric and clinical characteristics were measured using appropriate methods. Serum glucose was measured using glucose-oxidase method; lipid profile by enzymatic–colorimetric method.ResultsWaist hip ratio (WHR) was significantly higher in IFG–IGT and type 2 DM subjects. Systolic blood pressure was significantly higher in IFG–IGT and diastolic blood pressure is significantly higher in IGT, IFG–IGT and type 2 DM compared to controls. Fasting serum TG (p = 0.008) and cholesterol (p = 0.001) level was significantly higher in type 2 DM subjects but the values were not significantly different in prediabetic subjects compared to controls. HOMA B% and HOMA S% were significantly lower in DM and IFG–IGT subjects, IFG subjects have also shown significantly lower HOMA B% compared to controls.ConclusionThese results indicate that hypertension, central obesity (WHR) and insulin resistance, three major factors for metabolic syndrome are present in prediabetic condition in a Bangladeshi population.     

The relative contributions of insulin resistance and beta cell failure to the transition from normal to impaired glucose tolerance varies in different ethnic groups

AimTo evaluate ethnic differences in the contribution of decline in insulin secretion and insulin sensitivity in impaired glucose tolerance (IGT).MethodsSeven hundred and eighteen subjects of Arab, Japanese and Mexican American decent received oral glucose tolerance test (OGTT) with plasma glucose and insulin measurement every 30 min. The Matsuda index of insulin sensitivity and the relation between incremental increase under plasma insulin to glucose curves during the OGTT (ΔI_0–120/ΔG_0–120) were calculated.ResultsNGT Japanese subjects had highest insulin sensitivity index (7.1 ± 4.6) and lowest insulin secretion index ((ΔI_0–120/ΔG_0–120 = 1.1 ± 0.9). Mexican Americans and Arabs had lower insulin sensitivity (4.1 ± 2.8 and 3.5 ± 2.3, respectively) and higher insulin secretion indices (2.2 ± 2.0 and 2.5 ± 2.5). IGT subjects in all ethnic groups had reduced insulin sensitivity and insulin secretion compared to NTG subjects. However, the reduction in insulin sensitivity was the largest in Mexican American (30%), the smallest in Arabs (11.5%) and intermediate in Japanese (23%). Conversely, the decrease in insulin secretion was the greatest in Arabs (80%), the smallest in Mexican Americans (41%) and intermediate in Japanese (55%).In a multivariate regression analysis model, the decline in insulin secretion was a stronger determinant of 2-h plasma glucose in Arabs than the reduction in insulin sensitivity while the opposite was observed in Mexican Americans and Japanese.ConclusionDifferences in insulin sensitivity and insulin secretion are present amongst different ethnic groups. The relative contributions of reduced insulin action and impaired insulin secretion are likely to contribute differentially to progression from NGT to IGT (and diabetes) in different ethnic groups.     

Performance of glycated haemoglobin (HbA1c) as a screening test for diabetes and impaired glucose tolerance (IGT) in a high risk population—The Brazilian Xavante Indians

AimsTo examine the properties of HbA1c to detect diabetes and IGT in adult Brazilian Xavante Indians, a high risk population for diabetes.MethodsThe survey was carried out between October 2010 and January 2012 and based on a 75 g oral glucose tolerance test (OGTT). Basal and 2 h capillary glycaemia were measured by HemoCue Glucose 201+; HbA1c using an automated high-performance liquid chromatography analyzer (Tosoh G7).Results630 individuals aged ≥20 years were examined and 80 had a previous diagnosis of diabetes. Sensitivity, specificity and accuracy for HbA1c ≥ 6.5% (≥48 mmol/mol) were 71.3%, 90.5% and 87.2%. The areas under the ROC curve (AUC) was 0.88 (95%CI: 0.83–0.93). To identify IGT, HbA1c values between 5.7% and 6.4% (39–47 mmol/mol) presented sensitivity, specificity and accuracy of 87.2%, 24.7% and 51.4%, with an AUC of 0.62 (95%CI: 0.57–0.67).ConclusionsThe ADA/WHO proposed cut-off of 6.5% (48 mmol/mol) for HbA1c was adequate to detect diabetes among the Xavante. However, the performance of the ADA proposed cut-off points for pre-diabetes, when used to detect IGT was inadequate and should not be recommended.     

Evaluation of serum zonulin level in prediabetic patients

BackgroundThis study aimed to investigate the relationship between lipopolysaccharide (LPS) and zonulin levels and also to show the effect of acute hyperglycemic stress induced by oral glucose tolerance testing (OGTT) on zonulin levels in pre-diabetic patients.MethodsFour groups were constituted according to the criteria of the American Diabetes Association (ADA), based on OGTT results: control group (n:40); prediabetic group (n:56), divided into two subgroups: impaired fasting glucose group (IFG) (n:36), and impaired glucose tolerance (IGT) + IFG group (n:20) and type-2 diabetes mellitus (T2DM) group (n:45).ResultsZonulin and LPS did not significantly differ between the prediabetes and control groups, but were significantly higher in the T2DM group compared to both the prediabetic and the control group (P < 0.001). After OGTT, zonulin and LPS were significantly higher in the prediabetes group compared to the control group (P < 0.01 and P < 0.05, respectively), and significantly lower in the IFG and IFG + IGT groups compared to the T2DM group (P < 0.001, P < 0.001 and P < 0.001, P < 0.001, respectively). A positive correlation was detected between fasting zonulin and 2-hour zonulin (r = 0.727, P < 0.001) and between fasting LPS (r = 0.555, P < 0.001) and 2-hour LPS (r = 0.567, P < 0.001) in the prediabetic group. Increased zonulin and LPS levels and the positive correlation between these levels during the prediabetic period although non significant suggests onset of intestinal permeability.ConclusionsDuring acute hyperglycemia in prediabetic patients, up-regulation of zonulin and LPS may affect intestinal function. The intestines may play a key role in up-regulation of glucose and the pathogenesis of diabetes.     

Confirming Glycemic Status in the Diabetes Prevention Program: Implications for Diagnosing Diabetes in High Risk Adults

AimsTo examine the ability of fasting plasma glucose (FPG) and/or 2-h glucose to confirm diabetes and to determine the proportion of participants with HbA1c ≥ 6.5%.MethodsDiabetes confirmation rates were calculated after a single elevated FPG and/or 2-h glucose on an oral glucose tolerance test (OGTT) using a confirmatory OGTT performed within 6 weeks.Results772 (24%) participants had elevated FPG or 2-h glucose on an OGTT that triggered a confirmation visit. There were 101 triggers on FPG alone, 574 on 2-h glucose alone, and 97 on both. Only 47% of participants who triggered had confirmed diabetes. While the confirmation rate for FPG was higher than that for 2-h glucose, the larger number of 2-h glucose triggers resulted in 87% of confirmed cases triggering on 2-h glucose. Confirmation rates increased to 75% among persons with FPG ≥ 126 mg/dl and HbA1c ≥ 6.5%.ConclusionsOnly half of the persons with elevated FPG and IGT were subsequently confirmed to have diabetes. At current diagnostic levels, more persons trigger on 2-h glucose than on FPG, but fewer of these persons have their diagnoses confirmed. In individuals with FPG ≥ 126 mg/dl and HbA1c ≥ 6.5%, the confirmation rate was increased.     

Comparison of metabolic syndrome with glucose measurement for prediction of type 2 diabetes: The Isfahan Diabetes Prevention Study

AimsThe aim of this study was to compare the ability of the metabolic syndrome (MetS) and fasting and 2-h glucose to predict progression to diabetes in non-diabetic first-degree relatives (FDRs) of patients with type 2 diabetes.MethodsA total of 706 non-diabetics FDR 20–70 years old in 2003–2005 were followed through 2008 for the occurrence of type 2 diabetes mellitus. At baseline and through follow-ups, participants undergo a standard 75 g 2-h oral glucose tolerance test. MetS was defined by NCEP-ATP III.ResultsThe fasting and 2-h glucose values were better predictors of progression to diabetes than MetS. Compared to participants without MetS, the age-adjusted relative risk (RRs) of diabetes was similar for participants with MetS (1.09 (95% CI 0.92, 1.29)). The age-adjusted relative risk of diabetes among those with impaired glucose tolerance (IGT) and MetS was 1.89 (95% CI 1.47, 2.42) and among those with IGT but without MetS was 1.59 (95% CI 1.32, 1.91). Areas under the receiver operating characteristic curves were 0.789 for fasting and 0.760 for 2-h glucose versus 0.595 for number of metabolic abnormalities (P < 0.001).ConclusionsThese data indicate that fasting or 2-h glucose during the OGTT may be more effective and efficient than MetS in predicting progression to diabetes.     

Impaired glucose metabolism in hypertensive patients with/without the metabolic syndrome

BackgroundIn hypertension clinics, screening patients for the metabolic syndrome (MetS) is common practice, while performing the cumbersome oral glucose tolerance test (OGTT) is not. How large is the underestimation of diabetes and prediabetes that ensues is unknown.MethodsWe recruited N = 1397 patients with essential arterial hypertension who underwent a 75-g OGTT and were classified as normally glucotolerant (NGT) or having impaired glucose metabolism (IGM), and as affected or not by MetS (ATPIII criteria). The agreement between the OGTT and the ATPIII criteria in attributing a high cardiovascular risk was estimated by matching the categories of MetS and no-MetS with NGT and IGM.Resultsn = 677/1397 patients (48%) satisfied criteria for MetS, while n = 757/1397 (54%) had an IGM. MetS and IGM were both present in n = 512/1397 patients (36.6%), and both absent in n = 475/1397 (34%). Further n = 410/1397 patients (29%) were discordant for the two conditions: n = 165/410 (40%) had the MetS but were NGT, and n = 245/410 (60%) had IGM but no MetS. Among IGM patients, n = 168/757 (22%; of which 45 had no MetS) received a new diagnosis of diabetes based on OGTT criteria. Among all discordant patients, those with IGM and no MetS were more commonly males (p < 0.001), and had older age (p < 0.001) and lower body mass index (p < 0.05).ConclusionsAmong patients with hypertension, the estimate of the prevalence of diabetes and prediabetes, hence of the global cardiovascular risk, can be seriously flawed unless an OGTT is performed. Our results support a wider use of the OGTT in the management of hypertension.     

Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146

ObjectiveTCF7L2 variant rs7903146 is associated with increased risk for type 2 diabetes. We investigated the effect of TCF7L2 variant rs7903146 and glucose tolerance on free fatty acid (FFA) metabolism.Research Design and MethodsWe recruited 120 individuals, half homozygous for the major CC allele and half homozygous for the minor TT allele at rs7903146; each underwent a 2-h, 75 g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT.ResultsTotal FFA concentrations and percent FA species during OGTT were not different in CC and TT carriers when males and females were considered together. However, monounsaturated fatty acid (MUFA) concentrations and percentages were greater in TT than CC females during the OGTT. TT carriers with high HOMA-IR had significantly greater fasting FFA concentrations, lower disposition index (DI) and greater AUC of glucose than high HOMA-IR CC carriers, whereas no such differences were observed in the low HOMA-IR group. We found that fasting (826 ± 25 vs. 634 ± 22 μmol/L, P < 0.0001) and OGTT plasma FFA concentrations were greater in IGT than NGT subjects, and the difference remained after adjusting for sex, age, BMI, and genotype. Finally, IGT subjects had greater MUFA concentrations and percentages than NGT subjects during OGTT.ConclusionsDespite similar fasting insulin and glucose, fasting plasma FFA are greater in IGT than NGT adults. Insulin resistance and sex influence plasma FFA responses amongst carriers of the minor T allele of TCF7L2 rs7903146.     

Association between circadian rhythm of blood pressure and glucose tolerance status in normotensive,non-diabetic subjects

AimsTo examine whether circadian rhythm of blood pressure (BP) is associated with glucose tolerance status in normotensive, non-diabetic subjects.MethodsA cross-sectional study recruited normotensive and non-diabetic subjects, aged 35–79 years. A 75 g oral glucose tolerance test (OGTT) and 24-h ambulatory blood pressure monitoring (24-h ABPM) were performed.ResultsAmong 31 impaired glucose tolerance (IGT) and 36 normal glucose tolerance (NGT) study subjects, the mean (±S.D.) diurnal–nocturnal differences of average systolic BP (SBP) were 7.1 ± 6.9 and 9.9 ± 6.2 mm Hg, respectively (p = 0.086). In a linear mixed-effects regression model, however, taking each measurement of BP as the outcome, nighttime reduction of SBP in the IGT group was 7.19 mm Hg, which was significantly smaller compared to a reduction of 9.80 mm Hg in the NGT group (p-value for IGT: nighttime interaction = 0.0014). The prevalence of non-dipping BP pattern was 77.4% in the IGT group which was significantly higher than 52.8% of the NGT group (p = 0.036). Logistic regression revealed a significant effect of IGT for predicting non-dipping pattern with an adjusted odds ratio of 3.71 (95% CI: 1.09, 12.66, p = 0.029).ConclusionsAmong normotensive, non-diabetic subjects, the decreased nocturnal BP reduction was associated with impaired glucose tolerance status.     

Impact of body mass index and metabolic phenotypes on coronary artery disease according to glucose tolerance status

ObjectiveThis study aimed to examine the impact of obesity, as defined by body mass index (BMI), and a metabolically unhealthy phenotype on the development of coronary artery disease (CAD) according to glucose tolerance status.MethodsThis population-based retrospective cohort study included 123,746 Japanese men aged 18–72 years (normal glucose tolerance: 72,047; prediabetes: 39,633; diabetes: 12,066). Obesity was defined as a BMI ≥ 25 kg/m². Metabolically unhealthy individuals were defined as those with one or more of the following conditions: hypertension, hypertriglyceridaemia and/or low HDL cholesterol. A Cox proportional hazards regression model identified variables related to CAD incidence.ResultsThe prevalences of obese subjects with normal glucose tolerance, prediabetes and diabetes were 21%, 34% and 53%, whereas those for metabolically unhealthy people were 43%, 60% and 79%, respectively. Multivariate analysis showed that a metabolically unhealthy phenotype increases hazard ratios (HRs) for CAD compared with a metabolically healthy phenotype, regardless of glucose tolerance status (normal glucose tolerance: 1.98, 95% CI: 1.32–2.95; prediabetes: 2.91, 95% CI: 1.85–4.55; diabetes: 1.90, 95% CI: 1.18–3.06). HRs for CAD among metabolically unhealthy non-obese diabetes patients and obese diabetes patients with a metabolically unhealthy status were 6.14 (95% CI: 3.94–9.56) and 7.86 (95% CI: 5.21–11.9), respectively, compared with non-obese subjects with normal glucose tolerance and without a metabolically unhealthy status.ConclusionA metabolically unhealthy state can associate with CAD independently of obesity across all glucose tolerance stages. Clinicians may need to consider those with at least one or more conditions indicating a metabolically unhealthy state as being at high risk for CAD regardless of glucose tolerance status.     

Prevalence of impaired glucose tolerance in ischemic Egyptian patients

Background and aimPrediabetes (impaired glucose tolerance or impaired fasting glucose) is usually associated with a higher health risk profile for cardiovascular diseases. To our knowledge, no data about its prevalence in Egyptian patients are available. We aimed to determine the prevalence of prediabetes among Egyptian patients who were known to be neither diabetic nor prediabetic & referred to undergo coronary angiography.Methods and resultsThe study included 1000 consecutive Egyptians in the Cairo governorate with no previous diagnosis of diabetes nor prediabetes, who underwent coronary angiography for suspected coronary artery disease. They were screened for having prediabetes with either impaired fasting glucose through checking their fasting blood sugar or impaired glucose tolerance through checking their 2 h postprandial blood sugar.Twenty-three percent of patients had prediabetes; either isolated impaired fasting glucose, isolated impaired glucose tolerance or both combined together. The mean age of all patients was 52.35 ± 7.02 years. 26.33% of female patients were prediabetic while 21.43% of male patients were prediabetic. Hypertensive prediabetic patients numbered 110 and most of them were females. Body Mass Index among prediabetic patients was higher than that among patients with normal glucose tolerance and in females more than males. Prediabetes was more prevalent among patients with acute coronary syndrome than among patients with chronic ischemic heart disease.ConclusionPrediabetes is prevalent among ischemic Egyptian patients at a considerable ratio and should be screened for.     

Monofilament insensitivity and small and large nerve fiber symptoms in impaired fasting glucose

AimsTo determine if diabetes or pre-diabetes is associated with monofilament insensitivity and peripheral neuropathy symptoms.MethodsThe 10-g Semmes-Weinstein monofilament test and Michigan Neuropathy Screening Instrument symptom questionnaire were administered to participants in the Study of Women's Health Across the Nation – Michigan site (n = 396). We determined the concordance of monofilament insensitivity and symptoms and used chi-square tests, ANOVA, and logistic regression to quantify the relationships among diabetes status, monofilament insensitivity and symptoms.ResultsThe prevalence of monofilament insensitivity was 14.3% and 19.4% of women reported symptoms of peripheral neuropathy. With monofilament testing, 11.7% of women with normal fasting glucose, 14.4% of women with impaired fasting glucose (IFG) and 18.3% of women with diabetes had monofilament insensitivity (p-value = 0.33). For symptoms, 14.0% of women with normal fasting glucose, 16.5% of women with IFG and 31.2% of women with diabetes reported symptoms of peripheral neuropathy. Women who reported symptoms of small fiber nerve dysfunction alone were unlikely to have monofilament insensitivity. Compared to women with normal fasting glucose, women with diabetes were more likely to report peripheral neuropathy symptoms [OR 2.8 (95% CI: 1.5, 5.1)]. Women with diabetes were also more likely to report symptoms than women with IFG (p = 0.02). There was no difference in the frequency of symptoms between women with normal fasting glucose and IFG.ConclusionsWomen with diabetes were more likely to report peripheral neuropathy symptoms. The prevalence of monofilament insensitivity and peripheral neuropathy symptoms did not differ between women with normal fasting glucose and IFG.