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PubMed2006

Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men.

Type 2 diabetes mellitus (T2DM) is strongly associated with obesity in most, but not all, ethnic groups, suggesting important ethnic differences in disease susceptibility. Although it is clear that insulin resistance plays a major role in the pathogenesis of T2DM and that insulin resistance is strongly associated with increases in hepatic (HTG) and/or intramyocellular lipid content, little is known about the prevalence of insulin resistance and potential differences in intracellular lipid distribution among healthy, young, lean individuals of different ethnic groups. To examine this question, 482 young, lean, healthy, sedentary, nonsmoking Eastern Asians (n = 49), Asian-Indians (n = 59), Blacks (n = 48), Caucasians (n = 292), and Hispanics (n = 34) underwent an oral glucose tolerance test to assess whole-body insulin sensitivity by an insulin sensitivity index. In addition, intramyocellular lipid and HTG contents were measured by using proton magnetic resonance spectroscopy. The prevalence of insulin resistance, defined as the lower quartile of insulin sensitivity index, was approximately 2- to 3-fold higher in the Asian-Indians compared with all other ethnic groups, and this could entirely be attributed to a 3- to 4-fold increased prevalence of insulin resistance in Asian-Indian men. This increased prevalence of insulin resistance in the Asian-Indian men was associated with an approximately 2-fold increase in HTG content and plasma IL-6 concentrations compared with Caucasian men. These data demonstrate important ethnic and gender differences in the pathogenesis of insulin resistance in Asian-Indian men and have important therapeutic implications for treatment of T2DM and for the development of steatosis-related liver disease in this ethnic group.

Adipose Tissue↗
PubMed2005

Differentially expressed proteins in the pancreas of diet-induced diabetic mice.

The pancreas is a heterogeneous organ mixed with both exocrine and endocrine cells. The pancreas is involved in metabolic activities with the endocrine cells participating in the regulation of blood glucose, while the exocrine portion provides a compatible environment for the pancreatic islets and is responsible for secretion of digestive enzymes. The purpose of this study was to identify pancreatic proteins that are differentially expressed in normal mice and those with diet-induced type 2 diabetes (T2DM). In this study, C57BL/6J male mice fed a high fat diet became obese and developed T2DM. The pancreatic protein profiles were compared between control and diabetic mice using two-dimensional gel electrophoresis. Differentially expressed protein "spots" were identified by mass spectrometry. REG1 and REG2 proteins, which may be involved in the proliferation of pancreatic beta cells, were up-regulated very early in the progression of obese mice to T2DM. Glutathione peroxidase, which functions in the clearance of reactive oxidative species, was found to be down-regulated in the diabetic mice at later stages. The RNA levels encoding REG2 and glutathione peroxidase were compared by Northern blot analysis and were consistent to the changes in protein levels between diabetic and control mice. The up-regulation of REG1 and REG2 suggests the effort of the pancreas in trying to ameliorate the hyperglycemic condition by stimulating the proliferation of pancreatic beta cells and enhancing the subsequent insulin secretion. The down-regulation of glutathione peroxidase in pancreas could contribute to the progressive deterioration of beta cell function due to the hyperglycemia-induced oxidative stress.

Animals↗
PubMed2025

Treatment preference for once-weekly versus once-daily DPP-4 inhibitors in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/OBJECTIVE: Although once-weekly and once-daily DPP-4 inhibitors have gained widespread market recognition, patient preference differences remain a key focus. This meta-analysis compares treatment preferences for once-weekly versus once-daily DPP-4 inhibitors in T2DM, offering evidence to guide clinical decisions and healthcare policies. METHODS: PubMed, OVID, EBSCO, Web of Science, CNKI, Wanfang, and clinical trial registries were searched up to June 30, 2025. After screening literature against predefined criteria, a systematic review was conducted to compare the effects of once-weekly and once-daily DPP-4 inhibitors on the treatment preferences of patients with T2DM. RESULTS: 8 RCTs with 1,575 participants were analyzed. No significant difference in medication adherence and DTSQ total score between the once-weekly and once-daily groups (p > 0.05). HbA1c percentage (MD = -0.21, 95% CI [-0.42, -0.01], p < 0.05) decreased significantly with once-weekly dosing, while GA and FPG showed no change (p > 0.05), this suggests greater improvement in HbA1c percentage levels following a switch to once-weekly DPP-4 inhibitors. Once-weekly DPP-4 inhibitors showed higher musculoskeletal/connective tissue disorder risk (RR = 2.63; 95% CI [1.18, 5.83]), but no significant differences in other adverse events (p > 0.05). No significant differences in treatment burden between both groups (p > 0.05). CONCLUSION: No statistically significant association between treatment preferences for once-weekly versus once-daily DPP-4 inhibitors among T2DM patients and medication adherence, treatment satisfaction, glycemic level changes, safety, or treatment burden for these two dosing regimens. Further research is needed to elucidate the influence of physician prescribing behavior on these preferences.

Humans↗
PubMed2026

Lifestyle interventions to prevent gestational and type 2 diabetes among migrant women from low- and middle-income countries: a systematic review.

Migrant women from low- and middle-income countries (LMICs) living in high-income settings experience disproportionately high risk of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM). This review aimed to identify and synthesise culturally adapted lifestyle interventions for preventing or managing GDM and T2DM among migrant women from LMICs, focusing on intervention components, cultural adaptation strategies, and behavioural and metabolic outcomes. Five databases (PubMed, Embase, Scopus, CINAHL, Cochrane Central) were searched using Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 guidelines. Eligible studies included experimental designs involving lifestyle interventions delivered to migrant women from LMICs in high-income countries, reporting outcomes related to GDM or T2DM targeting behaviour change. Data were synthesised narratively; study quality was appraised using RoB2 for RCTs and a structured narrative approach for non-randomised designs. Certainty of evidence was evaluated using GRADE. Eight studies met the inclusion criteria. Sample sizes ranged from 28 to 641 participants. Intervention duration varied from 6&#x2009;weeks to 12&#x2009;months. Most interventions incorporated atleast one culturally tailored component, such as bilingual delivery, culturally adapted dietary education, or community-based engagement. Improvements were reported across dietary behaviours, physical activity, glycaemic measures, or diabetes-related knowledge; however, effect sizes were modest and inconsistent. Interventions combining dietary modification, physical activity, and culturally adapted delivery demonstrated greater improvements than exercise-only or digital-only programmes. Overall certainty of evidence ranged from low to moderate. Culturally adapted, multi-component lifestyle interventions show promise for improving behavioural and metabolic outcomes among migrant women from LMICs; however, the evidence base remains limited.

Humans↗
PubMed2004

Thiazolidinediones: a review of their mechanisms of insulin sensitization, therapeutic potential, clinical efficacy, and tolerability.

The thiazolidinediones (TZDs) rosiglitazone and pioglitazone are newer additions to the antidiabetic armamentarium and are indicated for the treatment of type 2 diabetes mellitus (T2DM) in the United States. The TZDs are peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists that provide clinically effective glycemic control and unique pharmacologic effects on multiple risk factors for T2DM-related morbidity, including improvement of insulin sensitivity and endothelial dysfunction, reduction of blood pressure, and amelioration of dyslipidemia. Weight gain and fluid retention occur with TZD therapy, especially when they are administered in higher doses and in combination with insulin. Although fluid retention associated with the use of TZDs is generally mild and reversible, these agents should not be used in patients with New York Heart Association Class III or IV heart failure symptoms. The findings of ongoing, long-term, prospective studies will clarify the role of the TZDs in the treatment of T2DM, particularly in terms of the durability of improvements in glycemic control, insulin sensitivity, pancreatic beta- cell function, and cardiovascular health.

Blood Glucose↗
PubMed2006

General practitioners may diagnose type 2 diabetes mellitus at an early disease stage in patients they know well.

BACKGROUND: Continuity of care may not only save time and money for the health care system, but may also be beneficial for the individual patient. How well GPs know their patients may potentially lead to an early diagnosis of a slowly progressive chronic disease like type 2 diabetes mellitus (T2DM). The aim of this paper is to investigate this hypothesis. METHODS: A cross-sectional, population-based study of 1136 patients newly diagnosed with T2DM by their GP. Our main outcomes were how well the GPs' knew their patients (questionnaire) and centralized analysis of glycosylated haemoglobin A(1c). Multivariate linear regression models were used to allow adjustment for confounding variables. RESULTS: GPs classified how well they knew their patients as being not well for 13.5% (153/1136) of their patients, as fairly well for 38.6% (438/1136) and as very well for 48.0% (545/1136). Patients whom the GPs classified as not knowing well had relatively high glycaemic levels compared with levels among other patients, a finding that was confirmed in multivariate linear regression models. CONCLUSIONS: Our data show that the glycaemic level among patients whom the GP characterize as knowing well or fairly well is relatively low compared with among patients whom the GP characterize as not knowing well. We suggest that this reflects a late diagnosis in these patients, and that GPs should be especially aware of undiagnosed T2DM among patients whom they do not know well.

Aged↗
PubMed2006

Feline models of type 2 diabetes mellitus.

Feline diabetes mellitus (FDM) closely resembles human type 2 diabetes mellitus (T2DM) in many respects including clinical, physiological, and pathological features of the disease. These features include age of onset of FDM in middle age, association with obesity, residual but declining insulin secretion, development of islet amyloid deposits, loss of approximately 50% of beta-cell mass, and development of complications in several organ systems including peripheral polyneuropathy and retinopathy. Many of the pathological aspects of the disease are also experimentally inducible, facilitating study of the pathogenesis of these lesions. Physiological aspects of FDM and obesity are also well studied in the cat and provide an excellent basis for comparative studies of human T2DM. The relatively short generation time of cats along with breed predispositions to development of FDM may allow for more rapid screening and identification of genetic markers for diabetes susceptibility. FDM, in both spontaneous and inducible forms, therefore provides a good animal model of human T2DM and may provide additional insights into the pathogenesis of this important condition.

Animals↗
PubMed2025

Causal relationship between frailty and diabetes subtypes: A bidirectional Mendelian randomization study.

Frailty and diabetes mellitus (DM) are closely linked, but their causal relationship remains unclear. This study aims to determine the bidirectional causal relationship between frailty and different DM subtypes using Mendelian randomization (MR). We performed a 2-sample MR analysis using summary statistics from large-scale genome-wide association studies. The inverse-variance weighting method was the primary analytical approach, with MR-Egger regression and weighted median methods for sensitivity analysis. Horizontal pleiotropy and heterogeneity were assessed using MR-PRESSO and Cochran Q test. Genetically predicted frailty was significantly associated with an increased risk of type 2 diabetes (T2DM) and gestational diabetes (GDM) (odds ratio [OR]&#x2005;=&#x2005;2.142, 95% confidence interval [CI]: 1.751-2.621, P&#x2005;<&#x2005;.001; OR&#x2005;=&#x2005;2.280, 95% CI: 1.368-3.800, P&#x2005;=&#x2005;.002), but no causal relationship was observed for type 1 diabetes or glycemic traits (P&#x2005;>&#x2005;.05). Conversely, genetically predicted type 1 diabetes, T2DM, GDM, and postprandial glucose levels (2-hour post-load glucose) increased the risk of frailty (OR&#x2005;=&#x2005;1.026, 95% CI: 1.014-1.038, P&#x2005;<&#x2005;.001; OR&#x2005;=&#x2005;1.046, 95% CI: 1.033-1.058, P&#x2005;<&#x2005;.001; OR&#x2005;=&#x2005;1.068, 95% CI: 1.040-1.096, P&#x2005;<&#x2005;.001; OR&#x2005;=&#x2005;1.095, 95% CI: 1.049-1.144, P&#x2005;<&#x2005;.001). Sensitivity analyses confirmed the robustness of these findings. This study provides genetic evidence supporting a bidirectional causal relationship between frailty and diabetes, particularly T2DM and GDM. These findings highlight the need for early frailty screening in diabetic patients and better metabolic management in frail populations.

Humans↗
PubMed2026

Effects of GLP-1 Receptor Agonists and Dual GIP/GLP-1 Receptor Agonists on Inflammatory and Metabolic Biomarkers in Type 2 Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual GIP/GLP-1 receptor agonists improve cardiovascular outcomes in type 2 diabetes mellitus (T2DM), but their effects on inflammatory and oxidative biomarkers are not fully defined. MATERIALS AND METHODS: We searched PubMed, Ovid MEDLINE, Scopus, Web of Science and the Cochrane Library from inception to 19 February 2026 for randomised controlled trials (RCTs) in adults with T2DM comparing a GLP-1RA or dual GIP/GLP-1 agonist with placebo or active therapy, and reporting C-reactive protein (CRP or high-sensitivity CRP [hs-CRP]), interleukin-6 (IL-6), tumour necrosis factor-&#x3b1; (TNF-&#x3b1;), monocyte chemoattractant protein-1 (MCP-1), malondialdehyde (MDA) or adiponectin. Random-effects meta-analyses were conducted using standardised mean differences (SMDs). RESULTS: Forty-one RCTs were included. GLP-1RAs significantly reduced CRP/hs-CRP (27 studies, 1991 participants; SMD -0.37, 95% CI -0.59 to -0.14) and MDA (3 studies, 272 participants; SMD -0.98, 95% CI -1.65 to -0.30), and increased adiponectin (16 studies, 1327 participants; SMD 0.30, 95% CI 0.13 to 0.46). Pooled effects on IL-6 (17 studies, 1068 participants; SMD -0.14, 95% CI -0.37 to 0.10), TNF-&#x3b1; (16 studies, 1164 participants; SMD -0.25, 95% CI -0.61 to 0.12) and MCP-1 (7 studies, 450 participants; SMD -0.27, 95% CI -0.58 to 0.03) were not statistically significant, although MCP-1 decreased in sensitivity analyses. Across biomarkers, heterogeneity was moderate to high. Two tirzepatide RCTs (562 participants) showed a significant reduction in IL-6 (SMD -0.28, 95% CI -0.47 to -0.09) and a non-significant trend towards lower CRP/hs-CRP. CONCLUSIONS: In adults with T2DM, incretin-based therapies consistently lower CRP/hs-CRP, reduce oxidative stress (MDA) and increase adiponectin, while effects on IL-6 and TNF-&#x3b1; are more variable. These data support a selective anti-inflammatory and metabolic regulatory profile of GLP-1-based therapy, but heterogeneity and limited data for some biomarkers warrant cautious interpretation and further mechanistic studies. TRIAL REGISTRATION: PROSPERO number: CRD420261321430.

Humans↗
PubMed2006

The IGF-I system and the renal and haemodynamic effects of losartan in normotensive patients with type 2 diabetes mellitus: a randomized clinical trial.

OBJECTIVE: Losartan has been shown to protect the diabetic kidney, at least partly independent of changes in blood pressure. Imbalances in the IGF-I system are associated with the development of diabetic nephropathy. We investigated whether renal as well as haemodynamic effects of losartan are associated with changes in the IGF-I system in normotensive patients with type 2 diabetes mellitus (T2DM). DESIGN AND PATIENTS: This randomized, double-blind placebo-controlled clinical trial involved 74 normotensive patients with T2DM and microalbuminuria. Thirty-eight patients were assigned to receive losartan and 36 patients were assigned to receive placebo for 10 weeks. MEASUREMENTS: Serum levels of total and free IGF-I, IGFBP-3, creatinine and haemoglobin A(1c) (HbA(1c)), as well as urinary albumin excretion rate, creatinine clearance and blood pressure, were measured prior to the start of treatment and after 10 weeks of treatment. RESULTS: At baseline, serum levels of IGFBP-3 were elevated and serum levels of free IGF-I were reduced. Losartan tended to reduce IGFBP-3 levels and to increase free IGF-I levels, although neither effect was statistically significant. These effects were more pronounced in a subanalysis of 18 losartan-treated patients with stable metabolic parameters, with a decrease in IGFBP-3 from 133.2 to 122.6 nmol/l (P=0.006) and an increase in free IGF-I levels by 8% (ns). Serum levels of total IGF-I were unaffected. The change in IGFBP-3 was inversely correlated to the change in creatinine clearance (r=-0.4; P=0.02). Total and free IGF-I inversely correlated to systolic blood pressure (r= -0.46; P=0.007 and r=0.26; P=0.14 respectively). Furthermore, changes in total IGF-I and IGFBP-3 correlated to changes in serum creatinine levels in the metabolically stable patients (r=0.58, P=0.02 and r=0.6, P=0.01, respectively). Changes in the IGF-I system were unrelated to a reduction in microalbuminuria associated with losartan. CONCLUSIONS: Losartan lowered the elevated levels of IGFBP-3, although only significantly in the metabolically stable patients. A tendency towards an increase in free IGF-I levels was also observed, but this change was small and not statistically significant. These changes were not related to reduction in microalbuminuria, but might contribute to effects of losartan on creatinine clearance and blood pressure of losartan in normotensive patients with T2DM.

Albuminuria↗
PubMed2006

Effects of growth hormone on insulin resistance and atherosclerotic risk factors in obese type 2 diabetic patients with poor glycaemic control.

OBJECTIVE: We aimed to evaluate the combined effects of GH treatment and diet restriction on lipolysis and anabolism, insulin resistance and atherosclerotic risk factors in obese patients with type 2 diabetes mellitus (T2DM). SUBJECTS: This randomized, double-blind, placebo-controlled study included 24 obese T2DM patients (male : female = 12 : 12, mean age 53.7 +/- 7.2 years) with poor glycaemic control (fasting plasma glucose 10.673 +/- 1.121 mmol/l, HbA(1C) 9.9 +/- 2.3%). Sixteen of these patients were treated with recombinant human GH (1-1.5 units/day, 5 days/week) while undergoing diet restriction and exercise for 12 weeks. METHODS: Anthropometric and bioelectrical impedance measurements were undertaken to determine the lean body mass and total body fat. Computed tomography (CT) was performed to estimate visceral and subcutaneous fat distribution at the umbilicus level and the muscle area of the midthigh. Insulin resistance was measured by the insulin tolerance test (ITT) and by the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: The ratios VSR (visceral fat area/subcutaneous fat area) and VMR (visceral fat area/thigh muscle area) were significantly decreased in the GH-treated group compared to the control group. An increase in lean body mass was observed in the GH-treated group. Levels of total cholesterol, triglyceride, free fatty acid (FFA), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) were significantly decreased after GH treatment. Fasting glucose levels decreased similarly (P < 0.05 anova) in both groups during the treatment period. Fasting C-peptide levels significantly increased, whereas insulin levels significantly decreased, in the GH-treated group, but no changes were observed in the control group. The insulin sensitivity index (ISI) was significantly increased in the GH-treated group (1.3 +/- 1.4 vs. 1.9 +/- 1.0%/min, P < 0.05). CONCLUSIONS: GH treatment in obese T2DM patients with poor glycaemic control is beneficial in decreasing the amount of visceral fats, and may therefore result in improvements in insulin resistance, atherosclerotic risk factors and dyslipidaemia.

Analysis of Variance↗
PubMed2006

A review of the economic evidence for acarbose in the prevention of diabetes and cardiovascular events in individuals with impaired glucose tolerance.

The highly prevalent, prediabetic condition of impaired glucose tolerance (IGT) confers a high risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). There is an emerging body of cost-effectiveness literature in the management of IGT. For acarbose, an alpha-glucosidase inhibitor, economic analyses have been conducted for Spain, Germany, Sweden and Canada. In Spain, acarbose was more effective and less costly (dominant) compared with placebo. In Germany, the cost per patient free of diabetes was under Pounds 800; acarbose was dominant for those at high risk for T2DM, CVD or both, and a similar outcome in the Swedish study. In Canada, acarbose was dominant compared with no intervention and very cost-effective compared with metformin [C Dollars 1798/life years gained (LYG)]. The particularly cost-effective outcomes or cost savings delivered by acarbose for IGT subjects at high risk for T2DM and/or CVD render an IGT-intervention program prioritised to such high-risk individuals an economically attractive strategy.

Acarbose↗
PubMed2005

Progression from normal glucose tolerance to type 2 diabetes in a young girl: longitudinal changes in insulin sensitivity and secretion assessed by the clamp technique and surrogate estimates.

The pathophysiology of type 2 diabetes (T2DM) involves insulin resistance and relative insulin deficiency in at-risk youth. We-report longitudinal changes in insulin sensitivity and secretion in a high-risk African-American youth with obesity and polycystic ovary syndrome who progressed from normal glucose tolerance to impaired glucose tolerance to T2DM within 5 yr. This report demonstrates that in our patient: (i) insulin resistance was the pre-existing abnormality, but it was the marked decline in insulin secretion which led to T2DM and (ii) surrogate estimates of insulin sensitivity using fasting glucose and insulin concentrations were not reliable indices in reflecting the changes in in vivo insulin sensitivity in this case.

Blood Glucose↗
PubMed2006

Elevated fasting triglycerides predict impaired glucose tolerance in adolescents at risk for type 2 diabetes.

OBJECTIVE: The aim of this study was to evaluate whether fasting laboratory values can predict impaired glucose tolerance (IGT) in adolescents who are at risk for developing type 2 diabetes mellitus (T2DM). HYPOTHESIS: Elevated fasting triglycerides, a marker for worsening insulin resistance, predict risk for IGT. DESIGN: Following a fast of at least 9 h, laboratory measures, body mass index (BMI), and demographic information were obtained. The subjects then underwent a 75-g oral glucose challenge with a 2-h postchallenge glucose determination. SUBJECTS: Eighty-four adolescents aged 12-20 yr with at least two risk factors for developing T2DM (obesity, family history of T2DM, or acanthosis nigricans) and with either a fasting insulin level > or =25 microU/mL or a homeostasis model assessment of insulin resistance (HOMA-IR) > or =3.5 were recruited for the study. RESULTS: Ten subjects (12%) had IGT [2-h glucose > or =140 mg/dL (7.77 mmol/L)], and 10 subjects (12%) had impaired fasting glucose [IFG; fasting glucose > or =100 mg/dL (5.55 mmol/L)]. However, only three (30%) subjects with IGT had IFG, though all subjects with IGT had a fasting triglyceride level > or =150 mg/dL (1.70 mmol/L). Of those subjects with elevated triglycerides, 29% had IGT. As a screening test to predict risk for IGT, elevated triglycerides >150 mg/dL had a sensitivity of 100% and a specificity of 68%. The positive predictive value was 29%, and the negative predictive value was 100%. CONCLUSIONS: Screening with fasting glucose alone would have missed 70% of subjects with IGT in this population of insulin-resistant adolescents. However, a fasting triglyceride level > or =150 mg/dL was strongly associated with IGT and may help to identify at-risk adolescents who should undergo formal glucose tolerance testing.

Adolescent↗
PubMed2004

Nateglinide alone or with metformin safely improves glycaemia to target in patients up to an age of 84.

AIM: To assess the effect of nateglinide on efficacy [fasting plasma glucose (FPG), postprandial plasma glucose (PPG) plasma glucose and HbA1c], tolerability and safety in patients with type 2 diabetes mellitus (T2Dm) on diet alone or on metformin in subjects up to an age of 84. METHODS: In an open-labelled 12-week, parallel study of 358 patients, aged 35-84 years with T2Dm, nateglinide was given as either monotherapy in patients previously on diet alone or low-dose sulfonylureas, which required washout before the study (group 1), or as an addition therapy in patients on steady dose of metformin (group 2). Nateglinide 120 mg was given before main meals. HbA1c, FPG and PPG values were taken at the time of breakfast at the beginning and the end of the study. RESULTS: HbA1c fell by a mean of 0.83%, 95% confidence interval (CI) (-0.97, -0.69) (p < 0.001) in group 1, and 0.67%, 95% CI (-0.77, -0.58) (p < 0.001) in group 2. There was a significant improvement in PPG in group 1 by a mean reduction of -3.47 mmol/l, 95% CI (-4.08, -2.87) (p < 0.0001) and in group 2 of -2.41 mmol/l, 95% CI (-2.84, -1.99) (p < 0.0001). There was an improvement in FPG of -1.2 mmol/l, 95% CI (-1.49, -0.81) (p < 0.0001) and -0.8 mmol/l, 95% CI -(1.07, -0.53) (p < 0.0001) in group 1 and 2 respectively. 44% of patients in group 1 and 34% in group 2 achieved target of HbA1c < 7.0 and 66% in group 1 and 59% in group 2 achieved of HbA1c < 7.5%. Only one subject on nateglinide and metformin was withdrawn due to the side effect of hypoglycaemia. No patient required third-party assistance nor was admitted to hospital due to hypoglycaemia. CONCLUSION: These data demonstrate that nateglinide is a safe and effective agent in treatment to target in patients with T2Dm up to an age of 84 years.

Adult↗
PubMed2006

IRS1, KCNJ11, PPARgamma2 and HNF-1alpha: do amino acid polymorphisms in these candidate genes support a shared aetiology between type 1 and type 2 diabetes?

AIMS: Type 1 diabetes mellitus (T1DM) is a chronic disorder primarily triggered by environmental and immunological factors in genetically susceptible individuals. Despite the fact that there are indications of common aetiological features of T1DM and type 2 diabetes (T2DM), variation in genes involved in insulin secretion and insulin signalling has to a large extent been ignored as potential modifiers in the pathogenesis of T1DM. Recent studies suggest, however, that proven T2DM susceptibility gene variants may be involved in the pathogenesis of T1DM. The objective of this study was to estimate the impact of four selected amino acid polymorphisms -IRS-1 Gly972Arg, Kir6.2 Glu23Lys, HNF-1alpha Ala98Val and PPARgamma2 Pro12Ala in a Danish population of T1DM families. METHODS: All variants were genotyped in 490 simplex- and multiplex-T1DM families applying polymerase chain reaction-restriction fragment length polymorphism, and results were evaluated by means of a transmission disequilibrium test (TDT) analysis. RESULTS: TDT analysis revealed that the Arg972 IRS-1, the Lys23 Kir6.2 and the Val98 HNF-1alpha variants were transmitted from heterozygous parents to affected probands at frequencies of 49.1%, 47.0% and 54.1%, respectively (p > 0.05 for all). This was similar to the rate of transmission to unaffected siblings. The transmission rate of the Ala12 PPARgamma2 variant to affected probands was 46.5% (p > 0.05) which differed significantly from the transmission to unaffected offspring (p = 0.024). A combined analysis of the present and published pertinent data of 1691 transmissions showed a significantly decreased transmission of the PPARgamma2 Ala12 allele to affected probands (p = 0.0045). CONCLUSIONS: The Pro12Ala variant of PPARgamma2 is associated with T1DM, the minor Ala allele conferring a reduced risk. This same finding has been reported in patients with T2DM.

Adolescent↗
PubMed2006

The metabolic syndrome in type 2 diabetes: When does it matter?

AIMS: Young adults with type 2 diabetes (T2Dm) present the clinician with the problem of when to start therapies for the primary prevention of vascular disease and how to identify those at most vascular risk. We examine whether the metabolic syndrome (MetS) can be a useful clinical tool to stratify vascular risk in this context. METHODS: Data were collected from 5928 subjects with T2Dm, and subjects were categorized as having MetS by World Health Organization criteria (body mass index criteria modified for Asians using >23 kg/m2). The prevalence of macrovascular disease was examined by MetS status and age. RESULTS: The overall MetS prevalence was 72.3%. MetS was associated with an increased prevalence of ischaemic heart disease (IHD) (17.2% MetS vs. 11.6% no MetS, p < 0.0001), coronary artery bypass graft (7.6 vs. 4.7%, p < 0.0003), peripheral vascular disease (PVD) (4.7 vs. 3.7%, p = 0.08) and stroke (6 vs. 3.9%, p = 0.002) across all age groups. MetS subjects had an IHD prevalence equivalent to that seen in subjects who were one decade older without MetS. The most significant impact of MetS was for the age group of 40-49 years with much lesser impact seen with progressively increasing age [odds ratio (OR) = 2.1 for IHD in MetS compared with no MetS at age 40-50 years, p < 0.05; falling progressively to OR = 1.5 at age >70 years, p > 0.05]. Similar trends were seen for coronary artery by-pass graft (CABG) and PVD. There was a strong relationship between the number of MetS risk factors and IHD prevalence (r = 0.99, p = 0.0001). CONCLUSIONS: These data suggest that MetS is particularly useful in stratifying vascular risk in younger T2Dm patients and in those with a high number of MetS components. For patients with MetS, especially those with a full house of MetS risk factors, commencing risk-lowering interventions 10 years earlier than their MetS-free counterparts could be considered.

Adult↗
PubMed2004

Prevention of Type 2 diabetes mellitus. A review of the evidence and its application in a UK setting.

Abstract Type 2 Diabetes mellitus (T2DM) is a complex metabolic, multifactorial disease, which affects the quality, quantity and style of life. People with T2DM have a life expectancy that can be shortened by as much as 15 years, with up to 75% dying of macrovascular complications. To reduce the impact of T2DM in the 21st century, we need an approach that not only optimally treats the person with established diabetes but also prevents diabetes from occurring in the first place. The best evidence for prevention of diabetes is for interventions that target individuals at highest risk. Targeting patients who have impaired glucose tolerance with lifestyle changes including physical activity and dietary factors has been shown to be effective in the Chinese, North American and Finnish populations. In order for such lifestyle interventions to be successful in other populations, they need to be culturally sensitive, individualized and sustained. Some pharmacological agents including metformin and acarbose have also been shown to be effective, although the profile of those who respond is different. There continues to be a need to develop and evaluate interventions that target communities and populations at risk in a UK setting.

Diabetes Mellitus, Type 2↗