Higher Fasting Plasma Glucose Concentrations Research Articles

Systemic Stressors and Retinal Microvascular Alterations in People Without Diabetes: The Kailuan Eye Study.

PurposeThe purpose of this study was to determine systemic stressors, including fasting plasma glucose (FPG), and other major atherosclerotic cardiovascular disease (ASCVD) risk factors of the retinal microvasculature in people without diabetes.MethodsThe Kailuan Eye Study enrolled applicants from the community-based longitudinal Kailuan Study. Applicants underwent optical coherence tomographic angiography (OCTA) and systemic examinations. Both the macula and optic disc were screened, whereas superficial capillary plexus (SCP), deep capillary plexus (DCP), foveal vessel density in the 300 µm ring (FD-300), and radial peripapillary capillaries (RPCs) density were measured in the study.ResultsThis study included 353 eligible applicants (mean age = 49.86 ± 11.41 years; 47% men; FPG =5.32 ± 1.19 mmol/L). Lower DCP density was associated with elder age (P = 0.001), male gender (P < 0.001), and higher FPG (P = 0.008). Male gender (P < 0.001), axial length (P < 0.001), and FPG (P = 0.029) were inversely associated with RPC density. Meanwhile, a higher FPG concentration was significantly correlated with lower DCP density (P = 0.006) and higher intraocular pressure (P = 0.006), after adjusting mean arterial blood pressure (P = 0.001) and sex (P = 0.042).ConclusionsDCP density showed a significantly negative correlation with FPG concentration in people without diabetes. These data suggest hyperglycemia could cause early retinal capillary alterations in patients without clinical signs of retinopathy and indicate the potential clinical applications of routine OCTA may be beneficial to screen for subclinical microvasculature and monitor patients with high risks of ASCVD.

A cross-sectional study to estimate the point prevalence of painful diabetic neuropathy in Eastern Libya

BackgroundPainful Diabetic Neuropathy (PDN) is a complication that affects up to one third of people living with diabetes. There is limited data on the prevalence of PDN from countries in the Middle East and North Africa. The aim of this study was to estimate the point prevalence of PDN in adults in Eastern Libya using the self-report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) pain scale.MethodsWe invited patients attending the Benghazi Diabetes Centre who had diabetes for ≥ 5 years to take part in the study. Patients provided consent and completed the Arabic S-LANSS. Anthropometrics, marital status, socioeconomic and education information was recoded and fasting plasma glucose concentration determined.ResultsFour hundred and fifty participants completed the study (age = 19 to 87 years, BMI = 17.6 to 44.2 kg/m2, 224 women). One hundred and ninety five participants (43.3%) reported pain in their lower limbs in the previous 6 months and 190/195 participants (97.4%) reported a S-LANSS score of ≥ 12 suggesting they had neuropathic pain characteristics. Thus, 42.2% (190/450) of participants with diabetes were categorised as experiencing pain with neuropathic characteristics. Mean ± SD duration of diabetes for participants with PDN (20.4 ± 6.5 years) was significantly higher compared with those without PDN (11.1 ± 4.6 years). Participants with PDN smoked tobacco for more years than those without pain (7.9 ± 12.3 years versus 1.1 ± 3.9 years respectively); had significantly higher fasting plasma glucose concentration (143.6 ± 29.3 mg/dl versus 120.0 ± 17.3 mg/dl) and had a significantly higher levels of education and employment status. The most significant predictors of PDN were duration of diabetes (OR = 25.85, 95% CI = 13.56–49.31), followed by smoking for men (OR = 8.28, 95% CI = 3.53–9.42), obesity (OR = 3.96, 95% CI = 2.25–6.96) and high fasting plasma glucose concentration (OR = 3.51, 95% CI = 1.99–6.21).ConclusionThe prevalence of PDN in people with diabetes in Eastern Libya was 42.2%. Risk factors for developing PDN were high fasting plasma glucose concentration, long duration of diabetes, and higher level of educational and employment status.

Prevalence and risk factors of impaired fasting glucose and diabetes among Chinese children and adolescents: a national observational study.

The prevalence of impaired fasting glucose (IFG) and diabetes mellitus (DM) has reportedly increased significantly among Chinese children and adolescents. We aimed to examine the prevalence of IFG and DM, the disparities in sex and region and related risk factors among Chinese children and adolescents. A total of 16 434 Chinese children aged 6-17 years were selected from a national cross-sectional survey, and fasting glucose was measured for all participants. Overall, mean fasting plasma glucose (FPG) concentration was (4·64 (sd 0·51)) mmol/l, and the prevalence of DM and IFG was 0·10 and 1·89 %, respectively. Compared with girls, boys had higher FPG concentration (4·69 v. 4·58 mmol/l, r 0·107, P<0·001) and IFG prevalence (2·67 v. 1·07 %, r φ 0·059, P<0·001). Compared with rural children and adolescents, urban children and adolescent had higher FPG concentration (4·65 v. 4·62 mmol/l, r 0·029, P<0·001) and DM prevalence (0·15 v. 0·05 %, r φ 0·016, P<0·01). In addition, self-reported fried foods intake and overweight/obesity were positively associated with IFG, and the proportion of consuming fried foods more than or equal to once per week and overweight/obesity prevalence in boys and urban children and adolescents were significantly higher than girls and rural children and adolescents, respectively (P<0·05). Although the prevalence of IFG and DM was relatively low in Chinese children and adolescents, sex and region disparities were observed, which may be associated with differences in overweight/obesity prevalence and dietary factors.

Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum

BackgroundImbalances of gut microbiota composition are linked to a range of metabolic perturbations. In the present study, we examined the gut microbiota of women with gestational diabetes mellitus (GDM) and normoglycaemic pregnant women in late pregnancy and about 8 months postpartum.MethodsGut microbiota profiles of women with GDM (n = 50) and healthy (n = 157) pregnant women in the third trimester and 8 months postpartum were assessed by 16S rRNA gene amplicon sequencing of the V1-V2 region. Insulin and glucose homeostasis were evaluated by a 75 g 2-h oral glucose tolerance test during and after pregnancy.ResultsGut microbiota of women with GDM was aberrant at multiple levels, including phylum and genus levels, compared with normoglycaemic pregnant women. Actinobacteria at phylum level and Collinsella, Rothia and Desulfovibrio at genus level had a higher abundance in the GDM cohort. Difference in abundance of 17 species-level operational taxonomic units (OTUs) during pregnancy was associated with GDM. After adjustment for pre-pregnancy body mass index (BMI), 5 of the 17 OTUs showed differential abundance in the GDM cohort compared with the normoglycaemic pregnant women with enrichment of species annotated to Faecalibacterium and Anaerotruncus and depletion of species annotated to Clostridium (sensu stricto) and to Veillonella. OTUs assigned to Akkermansia were associated with lower insulin sensitivity while Christensenella OTUs were associated with higher fasting plasma glucose concentration. OTU richness and Shannon index decreased from late pregnancy to postpartum regardless of metabolic status. About 8 months after delivery, the microbiota of women with previous GDM was still characterised by an aberrant composition. Thirteen OTUs were differentially abundant in women with previous GDM compared with women with previous normoglycaemic pregnancy.ConclusionGDM diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with normoglycaemic pregnant women, and 8 months after pregnancy, differences in the gut microbiota signatures are still detectable. The gut microbiota composition of women with GDM, both during and after pregnancy, resembles the aberrant microbiota composition reported in non-pregnant individuals with type 2 diabetes and associated intermediary metabolic traits.

Glucose but not insulin or insulin resistance is associated with memory performance in middle-aged non-diabetic women: a cross sectional study.

BackgroundElevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population.MethodsWe linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 ± 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method.ResultsA higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = −0.08, 95% CI −0.14; −0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity.ConclusionsThis indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.

The TCF7L2 rs7903146 polymorphism, dietary intakes and type 2 diabetes risk in an Algerian population.

BackgroundThe transcription factor 7-like 2 (TCF7L2) gene is the most significant genetic risk factor for type 2 diabetes (T2D). Association analyses were performed on participants (n = 751, aged between 30 and 64) in the ISOR population-based study in the city of Oran. Dietary intakes were estimated using a weekly food frequency questionnaire.ResultsThe T allele of the rs7903146 single nucleotide polymorphism (SNP) was associated with lower body weight (p = 0.02), lower BMI (p = 0.009), lower waist circumference (p = 0.01) and a lower waist-to-hip ratio (p = 0.02). The T allele was associated with a significantly higher risk of T2D (odds ratio (OR) (95% confidence interval) = 1.55 (1.09–2.20), p = 0.01) and this association was independent of BMI. When considering the T2D risk, there were nominal interactions between the rs7903146 SNP and dessert (p = 0.05) and milk intakes (p = 0.01). The T2D risk was greater in T allele carriers with high dessert and milk intakes (OR = 2.61 (1.51-4.52), p = 0.0006, and 2.46 (1.47-4.12), p = 0.0006, respectively). In subjects with a high dessert intake, the T allele was also associated with higher fasting plasma glucose concentrations (4.89 ± 0.46 mmol/L in TT subjects, 4.72 ± 0.48 mmol/L in CT subjects and 4.78 ± 0.51 mmol/L in CC subjects; p = 0.03).ConclusionsThe T allele of the rs7903146 SNP is associated with a significantly higher risk of T2D in an Algerian population. This association was further strengthened by a high dessert intake, suggesting that gene-diet interactions increase the T2D risk.

Beyond fasting plasma glucose: The association between coronary heart disease risk and postprandial glucose, postprandial insulin and insulin resistance in healthy, nondiabetic adults

ObjectivePrediabetes is defined by elevations of plasma glucose concentration, and is aimed at identifying individuals at increased risk of type 2 diabetes and coronary heart disease (CHD). However, since these individuals are also insulin resistant and hyperinsulinemic, we evaluated the association between several facets of carbohydrate metabolism and CHD risk profile in apparently healthy, nondiabetic individuals. MethodsPlasma glucose and insulin concentrations were measured before and at hourly intervals for eight hours after two test meals in 281 nondiabetic individuals. Insulin action was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. CHD risk was assessed by measurements of blood pressure and fasting lipoprotein profile. ResultsFor purposes of analysis, the population was divided into tertiles, and the results demonstrated that the greater the 1) fasting plasma glucose (FPG) concentration, 2) incremental plasma insulin response to meals, and 3) SSPG concentration, the more adverse the CHD risk profile (p<0.05). In contrast, the CHD risk profile did not significantly worsen with increases in the incremental plasma glucose response to meals. ConclusionsIn nondiabetic individuals, higher FPG concentrations, accentuated daylong incremental insulin responses to meals, and greater degrees of insulin resistance are each associated with worse CHD risk profile (higher blood pressures, higher triglycerides, and lower high density lipoprotein cholesterol concentrations). Interventional efforts aimed at decreasing CHD in such individuals should take these abnormalities into consideration.

Are Individuals with Type 2 Diabetes More Likely to Burn Carbohydrate Versus Fat for Energy?

Impaired fat oxidation has been associated with increased plasma free fatty acid concentrations, ectopic fat deposition and insulin resistance, which may contribute to the development of Type 2 Diabetes (T2D). The objective of this pilot study was to determine whether individuals with T2D presented with a greater proportion of carbohydrate (CHO burners) versus fat (fat burners) oxidation over a 24 hour period (RQ24). A second objective was to determine whether metabolic variables and metabolic flexibility (ability to shift from fat to CHO oxidation) differed between CHO and fat burners. RQ24 was measured in 10 participants with T2D using a whole body calorimetry unit. Participants were fed a standard diet (50% CHO, 20% protein, 30% fat) that was individually prescribed to maintain energy balance. Fasting and postprandial biochemical measures and body composition were assessed. Participants were classified as CHO burners if RQ24 ≥ 0.880 (n=7) and fat burners if RQ24 ≤ 0.865 (n=3). Fat burners had higher fasting plasma glucose concentrations than CHO burners (p = 0.045), while CHO burners showed a trend toward a greater central fat mass (p = 0.071) and higher systolic blood pressure (p = 0.052). Metabolic flexibility was not significantly different between CHO and fat burners. Differences in RQ24 existed in participants with T2D fed a standard diet, suggesting that there was a greater number that exhibited a higher proportion of CHO than fat oxidation over a 24 hour period. Fasting glucose, central body fat and resting blood pressure were associated with these differences.

High-Frequency Variant p.T60M in NaCl Cotransporter and Blood Pressure Variability in Han Chinese

Objective: Frequent studies have confirmed that homozygous or compound heterozygous loss-of-function mutation p.Thr60Met in NaCl cotransporter (NCC) lead to the salt-wasting Gitelman’s syndrome (GS) of hypotension. The finding that Thr60 is a key SPAK/OSR1 phosphorylation site on NCC also raises the possible importance of Thr60 in regulating the activity of NCC and blood pressure (BP). However, the association of heterozygous NCC mutation p.Thr60Met and BP has not yet been studied. Methods: We collected 38 heterozygous mutation p.Thr60Met carriers, respectively, from 14 GS families confirmed by our previous studies and 1,000 unrelated Han Chinese, and matched them pairwise (sex, age ±2 years and BMI ±1) with 38 unrelated healthy controls. BP and biochemistry data were obtained. Student’s t test and χ² test were used to compare the differences between these study subjects with the heterozygous variant p.T60M and the controls. p < 0.05 was considered statistically significant. Results p.Thr60Met carriers had markedly lower BP (systolic 110.3 ± 13.5 vs. 119.1 ± 15.0 mm Hg; diastolic 70.2 ± 7.0 vs. 75.4 ± 8.2 mm Hg, p < 0.01) than controls. p.Thr60Met heterozygotes had higher fasting plasma glucose concentration (5.35 ± 0.73 vs. 4.95 ± 0.69 mmol/l, p < 0.01). 14 carriers versus 6 control subjects had impaired fasting glucose (36.8 vs. 15.8%, p < 0.01), and p.Thr60Met carriers had higher 24-hour urinary sodium excretion than controls but not significantly (170.2 ± 35.6 vs. 159.5 ± 39.0 mmol, p = 0.10). Conclusions: The NCC mutation p.Thr60Met carriers in Han populations have markedly lower BP and slightly higher fasting plasma glucose compared with normal controls.

Diabetic modifier QTL, &lt;i&gt;Dbm4&lt;/i&gt;, affecting elevated fasting blood glucose concentrations in congenic mice

We have previously identified four significant quantitative trait loci (QTL) affecting plasma glucose concentrations on F(2) progeny of hypoinsulinemic diabetic Akita mice, heterozygous for the Ins2 gene Cys96Tyr mutation, and non-diabetic A/J mice, one of which on chromosome 15 named Dbm4 (diabetic modifier QTL 4) was shown to affect fasting plasma glucose concentrations with a maximum LOD score of 6.17. To estimate the influence of Dbm4 itself to the diabetes-related phenotypes, we constructed congenic strain with heterozygous Ins2 mutation using the Akita allele as donor of Dbm4 locus in the A/J genetic background, and measured quantitative traits including plasma glucose concentrations in glucose tolerance test (GTT). In this study, we found the Akita allele in Dbm4 was associated with higher fasting plasma glucose concentrations as in previous QTL analysis. According to gene expression assay, key enzymes of hepatic gluconeogenesis were expressed to the more increased degree in the liver of congenic mice compared to the A/J allele based control mice. Based on these results, we concluded that diabetic modifier gene(s) exist on Dbm4 locus affecting fasting plasma glucose concentrations via regulation of gluconeogenic gene expression in the hypoinsulinemic diabetic condition. Identification of the modifier gene responsible for Dbm4 would provide new drug development targets for human type 2 diabetes with hepatic insulin resistance.

Melatonin Receptor 1A Gene Polymorphism Associated with Polycystic Ovary Syndrome

Background/Aims: Melatonin receptor 1A (MTNR1A) gene is a regulator of circadian rhythms and reproductive processes. The MTNR1A gene is also a potential candidate gene of polycystic ovary syndrome (PCOS). The aim of the present study was to determine whether or not the MTNR1A gene polymorphism is associated with a predisposition to PCOS. Methods: The single nucleotide polymorphism (SNP) rs2119882 in the MTNR1A gene was detected in 482 patients with PCOS and 522 healthy Chinese Han women. Subsequently, the association of MTNR1A gene variants with plasma glucose, insulin levels during oral glucose tolerance tests (OGTTs) and hormone levels was investigated. Results: The frequencies of genotypes and allelotypes of SNP rs2119882 differed significantly between PCOS cases and healthy controls (p < 0.001 and p = 0.002, respectively). SNP rs2119882 was associated with higher fasting plasma glucose concentrations (p = 0.021) and OGTT-induced insulin release at 0, 30, 60, and 120 min (all p < 0.05) in PCOS cases, as well as an increased homeostasis model assessment for insulin resistance (p = 0.005). Conclusion: SNP rs2119882 is associated with PCOS.

Association of rs10830963 and rs10830962 SNPs in the melatonin receptor (MTNR1B) gene among Han Chinese women with polycystic ovary syndrome

The aim of the present study was to determine whether or not the 'melatonin receptor (MTNR1B)' gene polymorphisms are associated with a predisposition for polycystic ovary syndrome (PCOS). The single-nucleotide polymorphisms (SNPs), rs10830963 and rs10830962, in the MTNR1B gene were detected in 526 patients with PCOS and 547 healthy Chinese Han women. The association between MTNR1B gene variants and plasma glucose and insulin levels during the oral glucose tolerance test (OGTT) and hormone levels was investigated. The frequencies of three genotypes and two allelotypes of the SNP, rs10830963, differed significantly between women with PCOS and healthy controls (P < 0.001 and P < 0.001, respectively). The SNP, rs10830963, was significantly associated with higher fasting plasma glucose concentrations (P < 0.001) and increased the area under the curve of plasma glucose levels during the OGTT (P < 0.001), as well as increased homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.027). No significant differences were observed in the genotypes and allele distributions of rs10830962 polymorphisms between the PCOS and the control groups (P = 0.311 and P = 0.178, respectively). There was no significant difference in the clinical and the metabolic characteristics in women with PCOS with different genotypes in the SNP, rs10830962 (all P > 0.005). The present study suggest that the SNP, rs10830963, in the MTNR1B gene is not only associated with susceptibility to PCOS, but also contributes to the PCOS phenotype.

Polymorphisms within the Novel Type 2 Diabetes Risk Locus MTNR1B Determine β-Cell Function

BackgroundVery recently, a novel type 2 diabetes risk gene, i.e., MTNR1B, was identified and reported to affect fasting glycemia. Using our thoroughly phenotyped cohort of subjects at an increased risk for type 2 diabetes, we assessed the association of common genetic variation within the MTNR1B locus with obesity and prediabetes traits, namely impaired insulin secretion and insulin resistance.Methodology/Principal FindingsWe genotyped 1,578 non-diabetic subjects, metabolically characterized by oral glucose tolerance test, for five tagging single nucleotide polymorphisms (SNPs) covering 100% of common genetic variation (minor allele frequency >0.05) within the MTNR1B locus (rs10830962, rs4753426, rs12804291, rs10830963, rs3781638). In a subgroup (N = 513), insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and in a further subgroup (N = 301), glucose-stimulated insulin secretion was determined by intravenous glucose tolerance test. After appropriate adjustment for confounding variables and Bonferroni correction for multiple comparisons, none of the tagging SNPs was reliably associated with measures of adiposity. SNPs rs10830962, rs4753426, and rs10830963 were significantly associated with higher fasting plasma glucose concentrations (p<0.0001) and reduced OGTT- and IVGTT-induced insulin release (p≤0.0007 and p≤0.01, respectively). By contrast, SNP rs3781638 displayed significant association with lower fasting plasma glucose levels and increased OGTT-induced insulin release (p<0.0001 and p≤0.0002, respectively). Moreover, SNP rs3781638 revealed significant association with elevated fasting- and OGTT-derived insulin sensitivity (p≤0.0021). None of the MTNR1B tagging SNPs altered proinsulin-to-insulin conversion.Conclusions/SignificanceIn conclusion, common genetic variation within MTNR1B determines glucose-stimulated insulin secretion and plasma glucose concentrations. Their impact on β-cell function might represent the prevailing pathomechanism how MTNR1B variants increase the type 2 diabetes risk.

Heterozygous mutations of the sodium chloride cotransporter in Chinese children: prevalence and association with blood pressure

Gitelman's syndrome (GS), which is caused by homozygous or compound heterozygous mutations of the thiazide-sensitive sodium chloride cotransporter (NCC), usually manifests in children and is associated with low blood pressure. However, the prevalence of heterozygous NCC mutations and their association with blood pressure in children have not yet been studied. Five hundred unrelated children from the Taipei Children Heart Study were enrolled. Genomic DNA was isolated from peripheral blood and the SLC12A3 gene was amplified by polymerase chain reaction (PCR). The 15 NCC mutations previously identified in Chinese patients with GS were evaluated using restriction fragment length polymorphism (RFLP) analysis. Blood pressure, biochemistry and urine pH were measured. The allelic frequency of heterozygous NCC mutations and their association with low blood pressure were also investigated. RFLP analysis for the 15 NCC mutations revealed heterozygous T60M in 1 child, T163M in 1, S283Y in 4, R642C in 2, W844X in 2, R928C in 9 and R959frameshift in 10 children. The overall incidence of positive heterozygous NCC mutations was approximately 2.9%. There were no significant differences in systolic or diastolic blood pressure, biochemical profiles or urine pH between children with heterozygous NCC mutations (n = 29) and non-affected controls (n = 471), except for slightly higher fasting plasma glucose concentrations in NCC-heterozygous children (91 +/- 2.3 versus 88 +/- 0.4 mg/dL, P < 0.05). Examination among the different NCC mutations showed that these children also had comparable blood pressures. We found a relatively high prevalence of heterozygous NCC mutations in Chinese children, suggesting that GS may not be rare in this population. Heterozygous NCC mutations were not associated with lower blood pressure in these Chinese children.

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.

Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure

Gitelmańs syndrome (GS) is an inherited recessive disorder caused by homozygous or compound heterozygous loss of function mutations of the NaCl cotransporter (NCCT) gene encoding the kidney-expressed NCCT, the pharmacological target of thiazide diuretics. An observational study estimated the prevalence of GS to 19/1,000,000, in Sweden, suggesting that approximately 1% of the population carries one mutant NCCT allele. As the phenotype of GS patients, who always carry two mutant alleles, is indistinguishable from that seen in patients treated with high-dose thiazide diuretics, we aimed at investigating whether subjects carrying one mutated NCCT allele have a phenotype resembling that of treatment with low-dose thiazide diuretics. We screened first-degree relatives of 18 of our patients with an established clinical end genetic diagnosis of GS for NCCT loss of function mutations and identified 35 healthy subjects carrying one mutant allele (GS-heterozygotes). Each GS-heterozygote was assigned a healthy control subject matched for age, BMI and sex. GS-heterozygotes had markedly lower blood pressure (systolic 103.3 +/- 16.4 versus 123.2 +/- 19.4 mmHg; diastolic 62.5 +/- 10.5 versus 73.1 +/- 9.4 mmHg; P < 0.001) than controls. There was no significant difference between the groups either in plasma concentration or urinary excretion rate of electrolytes, however, GS-heterozygotes had higher fasting plasma glucose concentration. Similar to patients being treated with low-dose thiazide diuretics, GS-heterozygotes have markedly lower blood pressure and slightly higher fasting plasma glucose compared with control subjects. Our findings suggest that GS-heterozygotes, the prevalence of which can be estimated to 1%, are partially protected from hypertension through partial genetic loss of function of the NCCT. However, as our study had a case-control design, it is important to underline that any potential effects on population blood pressure and risk of future cardiovascular disease need to be examined in prospective and population-based studies.

Effect of Testosterone on Insulin Sensitivity in Men with Idiopathic Hypogonadotropic Hypogonadism

To assess the presence of insulin resistance (IR) among a homogeneous cohort of male patients with idiopathic hypogonadotropic hypogonadism (IHH) and to investigate the effects of testosterone therapy on IR in this specific group. Twenty-four male patients with untreated IHH and 20 age-, sex-, and weight-matched eugonadal healthy control subjects were recruited for the study. Plasma glucose, plasma insulin, total and free testosterone, follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone-binding globulin levels were measured in fasting blood samples, and biochemical and hormonal analyses were performed for all study participants. IR was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula and the quantitative insulin sensitivity check index (QUICKI). Body mass index was calculated by weighing and measuring the heights of all study participants at the beginning of the investigation. Body fat mass and body lean mass were calculated as percentages of body weight by bioelectrical impedance analysis of body composition. Sustanon 250 (a combination of 4 testosterones) was administered intramuscularly once every 3 weeks for 6 months to male patients with IHH after a basal anthropometric, biochemical, and hormonal evaluation. The response to therapy was monitored by regular clinical examinations and serum testosterone measurements. After 6 months of testosterone treatment, the entire anthropometric, biochemical, and hormonal evaluation was repeated 14 days after the last injection of testosterone. Before treatment, male patients with IHH had higher fasting plasma glucose concentrations, higher fasting plasma insulin levels, a higher HOMA-IR score, and a lower QUICKI when compared with the control group. After testosterone treatment in the patient group, the HOMA-IR score decreased dramatically to the level in the control group. The high body fat mass of the male patients with IHH was reduced significantly after testosterone treatment, concomitant with significant increases in body mass index and body lean mass. Insulin sensitivity improves and body fat mass decreases with long-term testosterone replacement therapy.

Peroxisome proliferator‐activated receptor (PPAR) delta genetic polymorphism and its association with insulin resistance index and fasting plasma glucose concentrations in Chinese subjects

Previous studies have shown that the peroxisome proliferator-activated receptor delta (PPARD) genetic polymorphism affects cholesterol metabolism in Whites. This association was not observed in a Korean population in a separate study, but this study showed a link between the PPARD polymorphism and body weight and fasting plasma glucose. The purpose of this study was to determine whether polymorphisms of PPARD influence glucose and cholesterol metabolism in Chinese subjects. We investigated the association between the polymorphism (-87T/C) of the human PPARD gene and phenotypes related to body weight, insulin sensitivity, glucose and lipid metabolism in Chinese subjects. Unrelated Chinese subjects (n = 663) in Shanghai were studied; 287 had newly diagnosed Type 2 diabetes mellitus and 376 were non-diabetic control subjects over 40 years old. Clinical parameters were collected and genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. In normal glucose tolerant (NGT) subjects, the C allele carriers had higher fasting plasma glucose concentrations (P = 0.0078) and a lower insulin sensitivity index (ISI) (P = 0.0365). The C allele carriers also showed higher concentrations of low-density lipoprotein cholesterol (P = 0.0261) and percentage of body fat (P = 0.0357). There was a trend towards higher visceral adiposity in C allele carriers, but the difference was not significant (P = 0.0830). In diabetes patients, similar results were detected for plasma glucose concentrations (fasting plasma glucose P < 0.0001, 2-h plasma glucose P = 0.0052) and insulin sensitivity (homeostasis model assessment of insulin resistance P = 0.0094; ISI P = 0.0058). The PPARD-87T/C polymorphism is associated with higher fasting plasma glucose concentrations in both NGT and diabetic subjects, largely due to impaired insulin sensitivity.

Serum cholesteryl fatty acid composition and plasma glucose concentrations in Amerindian women

Diabetes mellitus has reached epidemic proportions in women of Amerindian origin. The risk of developing diabetes has been found to be related to the serum fatty acid composition in whites. We prospectively investigated the relation between the serum cholesteryl fatty acid composition and changes in fasting plasma glucose concentrations in Peruvian Indian women who are characterized by hyperinsulinemia in comparison to white women. A 5-y follow-up study of 73 women with normal fasting plasma glucose values was undertaken by performing a survey in 1999 and a follow-up survey in 2004. The studied variables included anthropometric measurements, plasma insulin and leptin, dietary food consumption from 24-h recall, blood pressure, and serum fatty acid composition. The participants developed significantly higher fasting plasma glucose concentrations in 2004 compared with 1999 (P < 0.0001) with unaltered plasma insulin values. Palmitoleic acid (16:1n-7) in 1999 was the only fatty acid that was significantly correlated to glucose concentration at follow-up. In a multiple regression analysis that included waist circumference, percentage of body fat, systolic blood pressure, and circulating triacylglycerol, insulin, leptin, and 16:1n-7 as independent determinants, 16:1n-7 and systolic blood pressure were the only significant determinants of plasma glucose concentration 5 y later. A high proportion of 16:1n-7 in serum is an independent predictor of high plasma glucose concentrations in Amerindian women. The reason for this association remains to be elucidated.

Immunological abnormalities in islets at diagnosis paralleled further deterioration of glycaemic control in patients with recent-onset Type I (insulin-dependent) diabetes mellitus.

To determine whether the clinical heterogeneity observed in the development of Type I (insulin-dependent) diabetes mellitus correlates with immunohistochemical differences observed at diagnosis. Patients (n = 17) with recent-onset diabetes clinically considered to be insulin dependent (Type I), underwent pancreatic biopsy for immunohistological analysis. These patients were divided into two groups based on the presence or absence of islet immunological abnormalities (insulitis or hyperexpression of MHC class I antigens or both). The patients were also HLA typed and tested for islet cell antibodies and antibodies to glutamic acid decarboxylase (GAD-Ab). All patients were followed monthly for 2 years and their fasting plasma glucose, haemoglobin A1c and daily insulin doses were recorded. The clinical course of patients with islet immunological abnormalities was compared with that of patients without those abnormalities. Patients with and without islet immunological abnormalities did not differ with regard to HLA type or islet cell antibodies. Antibodies to glutamic acid decarboxylase correlated with the presence of insulitis and MHC class I hyperexpression. These local immunological abnormalities were also associated with higher haemoglobin A1c values (p < 0.05) and a trend towards greater insulin requirements. Further, patients with the islet abnormalities had higher fasting plasma glucose concentrations 2 years after the biopsy than at the time of the biopsy (p < 0.05). The heterogeneous clinical course observed following diagnosis in patients with Type I diabetes correlates with islet immunological abnormalities. Insulitis and hyperexpression of MHC class I correlate with deteriorating glycaemic control.