Maximum body mass index before onset of type 2 diabetes is independently associated with advanced diabetic complications

IntroductionThe maximum body mass index (BMI) before onset of type 2 diabetes (MBBO) might be used to estimate a patient’s insulin secretion capacity. There have been few factors that can predict future diabetic complications at the time of diagnosis of diabetes mellitus. This study aimed to clarify the clinical usefulness of MBBO for predicting the development of advanced diabetic microvascular complications.Research design and methodsThis was a cross-sectional observational study. Of 1304 consecutively admitted patients with type 2 diabetes, we enrolled 435 patients for whom we could confirm their MBBO. Univariate and multivariate logistic regression analyses were performed to examine whether MBBO or BMI on admission was associated with advanced diabetic retinopathy or nephropathy. To evaluate the predictive performance of these indexes, we performed cross-validation in various models with MBBO or BMI and evaluated the areas under the curve (AUCs) yielded by these analyses.ResultsUnivariate analyses suggested that MBBO was associated with advanced retinopathy and nephropathy, while BMI on admission was associated only with advanced nephropathy. In multivariate analyses, MBBO was significantly associated with advanced complications, while BMI on admission was not. For advanced diabetic retinopathy, the AUCs were 0.70–0.72, and for advanced nephropathy, the AUCs were 0.81–0.83. When comparing the AUCs among models, the models with MBBO sustained high predictive performance for diabetic complications.ConclusionsMBBO was independently associated with advanced diabetic complications, while BMI on admission was not. Diabetic microvascular complications in patients with high MBBO could progress more rapidly. At the time of the diagnosis of diabetes mellitus, MBBO would enable us to predict the progress of diabetic complications.

Prognostic models of diabetic microvascular complications: a systematic review and meta-analysis

Background Many prognostic models of diabetic microvascular complications have been developed, but their performances still varies. Therefore, we conducted a systematic review and meta-analysis to summarise the performances of the existing models. Methods Prognostic models of diabetic microvascular complications were retrieved from PubMed and Scopus up to 31 December 2020. Studies were selected, if they developed or internally/externally validated models of any microvascular complication in type 2 diabetes (T2D). Results In total, 71 studies were eligible, of which 32, 30 and 18 studies initially developed prognostic model for diabetic retinopathy (DR), chronic kidney disease (CKD) and end stage renal disease (ESRD) with the number of derived equations of 84, 96 and 51, respectively. Most models were derived-phases, some were internal and external validations. Common predictors were age, sex, HbA1c, diabetic duration, SBP and BMI. Traditional statistical models (i.e. Cox and logit regression) were mostly applied, otherwise machine learning. In cohorts, the discriminative performance in derived-logit was pooled with C statistics of 0.82 (0.73‑0.92) for DR and 0.78 (0.74‑0.83) for CKD. Pooled Cox regression yielded 0.75 (0.74‑0.77), 0.78 (0.74‑0.82) and 0.87 (0.84‑0.89) for DR, CKD and ESRD, respectively. External validation performances were sufficiently pooled with 0.81 (0.78‑0.83), 0.75 (0.67‑0.84) and 0.87 (0.85‑0.88) for DR, CKD and ESRD, respectively. Conclusions Several prognostic models were developed, but less were externally validated. A few studies derived the models by using appropriate methods and were satisfactory reported. More external validations and impact analyses are required before applying these models in clinical practice. Systematic review registration PROSPERO CRD42018105287

RANTES 59029A/G Polymorphisms Associated with Diabetic Compilations in Korean Patients with Type 2 Diabetes for over 15 Years

Background: Polymorphisms in the RANTES gene are known to be associated with several diseases related to insulin resistance. In this study, we investigated the association between RANTES 59029A/G polymorphisms and the prevalence of diabetic complications relative to obesity in Korean patients who had type 2 diabetes (T2D) for over 15 years. Methods: A single-center, retrospective case-control study was performed. We included 271 patients with a duration of diabetes greater than 15 years. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze RANTES polymorphisms, identifying genotypes as GG, AG, or AA. Obesity was defined using the body mass index with a cutoff value of 25 kg/m2. Both microvascular (retinopathy and nephropathy) and macrovascular (coronary artery disease and cerebrovascular disease) complications were evaluated. Results: The duration of T2D and hemoglobin A1c values at enrollment were 24.4 ± 5.0 years and 7.8 ± 1.6%, respectively, in the non-obese group, and 25.4 ± 6.1 years and 7.7 ± 1.7%, respectively, in the obese group. The prevalence of microvascular complications was significantly higher in the obese group compared with that in the non-obese group (83.5% vs. 72.0%, p = 0.039). Compared to the non-obese group, the obese group showed a higher proportion of the patients with AA or AG genotypes (64.3% vs. 84.5%, p = 0.001). Conclusions: The A allele of the RANTES gene is associated with obesity and may affect diabetic microvascular complications in patients with T2D for over 15 years.

The Role of Biofactors in Diabetic Microvascular Complications

: Microvascular complications are responsible for a major proportion of the burden associated with diabetes contributing to substantial morbidity, mortality, and healthcare costs in people with diabetes. Retinopathy, nephropathy, and neuropathy constitute the leading causes of blindness, end-stage renal disease, and lower-extremity amputations, respectively. Since the efficacy of causal therapies of diabetic microvascular complications is limited, especially in type 2 diabetes, there is an unmet need for adjunct treatments which should be effective despite ongoing hyperglycemia. Experimental studies indicate that diabetic microvascular complications can be prevented or ameliorated by various biofactors in animal models by interfering with the pathophysiology of the underlying condition. Some of the findings related to biofactors like α-lipoic acid and benfotiamine could be translated into the clinical arena and confirmed in clinical trials, especially in those focusing on diabetic polyneuropathy. Given the micronutrient nature of these compounds, their safety profile is excellent. Thus, they have the potential to favorably modify the natural history of the underlying complication, but large long-term clinical trials are required to confirm this notion. Ultimately, biofactors should expand our therapeutic armamentarium against these common, debilitating, and even life-threatening sequelae of diabetes.

Mean Platelet Volume and Platelet Distribution Width Correlate with Microvascular Complications in Egyptian People with Type 2 Diabetes Mellitus

Background: Type 2 diabetes is a part of metabolic syndrome associated with a higher risk of vascular complications. Diabetes is characterized by changes in platelet morphology, function, and platelet hyperactivity so, it's considered a prothrombotic condition. Morbidity and mortality in people with type 2 diabetes-related to micro and macrovascular complications. Novel biomarkers are needed to identify and treat people at higher risk. Objective: The main objective of this controlled cross-sectional study was to evaluate Platelet volume indices (PVI) in subjects with type 2 diabetes with and without complications in comparison to subjects without diabetes. Methods: Hundred and thirty-five subjects aged from 35 to 60 years were subdivided into 3 groups. Group A includes 55 subjects with type 2 diabetes with complications. Group B includes 45 subjects with type 2 diabetes without complications. Group C includes 35 normal healthy subjects. Detailed clinical history was taken. Also, PVI, fasting blood glucose (FBG), hemoglobin A1c, and creatinine were obtained. Results: Mean Platelet Volume (MPV), Platelet Distribution Width (PDW), Plateletcrit (PCT), and Platelet large cell ratio (P-LCR) were significantly higher among subjects with retinopathy, nephropathy, and neuropathy than other subjects with diabetes who didn't develop complications (P<0.001). At cutoff value > 11.9 fL, MPV have diagnostic sensitivity 80% and specificity 97.8%. Whereas PDW >16.9fL has a sensitivity of 74.5% and specificity of 100% for diabetic microvascular complications (retinopathy, nephropathy, and neuropathy). Conclusion: MPV and PDW may be considered as possible biomarkers for the early detection of diabetic microvascular complications.

TCF7L2 Gene Polymorphism as a Risk for Type 2 Diabetes Mellitus and Diabetic Microvascular Complications

Background: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic condition with various genetics and environmental influences that affects the capacity of the body to produce or use insulin resulting in hyperglycemia, which may lead to variable complications. It is one of the world’s rising health problems. There is emerging evidence that some genetic polymorphisms can impact the risk of evolving T2DM. We try to determine the relationship of (rs7903146) variant of the Transcription factor 7-like 2 (TCF7L2) gene with T2DM and its microvascular complications.Methods and Results: This case-control study included 180 subjects: 60 diabetic patients without complications, 60 diabetic patients with microvascular complications and 60 matched healthy controls. Genotypes of rs7903146 (C/T) SNP in the TCF7L2 gene were evaluated by real-time polymerase chain reaction via TaqMan allelic discrimination. Logistic regression was used to detect the most independent factor for development of diabetes and diabetic microvascular complications. Variant homozygous TT and heterozygous TC genotypes were significantly increased in diabetic without complications and diabetic with complications groups than controls (p=0.003, 0.001) respectively. The T allele was more represented in both patient groups than controls with no significant difference between patient groups. TT genotype as well as T allele was significantly associated with increased T2DM risk.Conclusion: The T allele of rs7903146 polymorphism of TCF7L2 confers susceptibility to development of T2DM. However, no significant association was found for diabetic complications.