Offspring Of Diabetic Parents Research Articles

Paving the way for evidence-based population screening for type 1 diabetes.

Since the 1980s, we have been gaining knowledge about the pathogenesis of type 1 diabetes and found that the measurement of diabetes-associated autoantibodies against insulin, glutamic acid decarboxylase, insulinoma-associated protein 2, and zinc transporter 8 has a central role in recognition of early stages of the disease in asymptomatic people. In the 1990s, large prospective studies were established in Finland (the Diabetes Prediction and Prevention [DIPP] study 1 Kupila A Muona P Simell T et al. Feasibility of genetic and immunological prediction of type I diabetes in a population-based birth cohort. Diabetologia. 2001; 44: 290-297 Crossref PubMed Scopus (268) Google Scholar ), Germany (the BABYDIAB study 2 Ziegler AG Hummel M Schenker M Bonifacio E Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB study. Diabetes. 1999; 48: 460-468 Crossref PubMed Scopus (536) Google Scholar ), Sweden (Diabetes Prediction in Skåne Study 3 Elding Larsson H A Swedish approach to the prevention of type 1 diabetes. Pediatr Diabetes. 2016; 17: 73-77 Crossref PubMed Scopus (13) Google Scholar ), and the USA (the Diabetes Autoimmunity Study in the Young [DAISY] 4 Rewers M Bugawan TL Norris JM et al. Newborn screening for HLA markers associated with IDDM: Diabetes Autoimmunity Study in the Young (DAISY). Diabetologia. 1996; 39: 807-812 Crossref PubMed Scopus (349) Google Scholar ) that followed up children with a high genetic risk of developing type 1 diabetes from birth until diagnosis of clinical type 1 diabetes. On the basis of these findings, confirmed positivity for multiple (at least two) autoantibodies predicts almost inevitable progression to clinical type 1 diabetes within 15 years from seroconversion 5 Insel RA Dunne JL Atkinson MA et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015; 38: 1964-1974 Crossref PubMed Scopus (473) Google Scholar and thus allows the diagnosis before clinical symptoms develop. However, the disease's progression shows a high variability and mostly depends on the age at which seroconversion occurs, with prechoolers having a faster decline of residual β-cell function than adolescents. Therefore, to better understand the interaction between genetics and environmental factors in children with a high genetic risk of type 1 diabetes, further large prospective studies, such as TEDDY 6 TEDDY Study GroupThe Environmental Determinants of Diabetes in the Young (TEDDY) study: study design. Pediatr Diabetes. 2007; 8: 286-298 Crossref PubMed Scopus (219) Google Scholar or Diabetes Evaluation in Washington (DEW‑IT), 7 Wion E Brantley M Stevens J et al. Population-wide infant screening for HLA-based type 1 diabetes risk via dried blood spots from the public health infrastructure. Ann NY Acad Sci. 2003; 1005: 400-403 Crossref PubMed Scopus (24) Google Scholar were established in the USA in the early 2000s. Although maximum autoantibody conversion occurs between the first and second year of life, approximately 20% of children develop multiple antibodies after 5 years of age. Islet autoantibody screening in at-risk adolescents to predict type 1 diabetes until young adulthood: a prospective cohort studyScreening of adolescents at risk for type 1 diabetes only once at 10 years of age for islet autoantibodies was highly effective to detect type 1 diabetes by the age of 18 years, which in turn could enable prevention of diabetic ketoacidosis and participation in secondary prevention trials. Full-Text PDF

Comparison of Effect of Exercise on Insulin Sensitivity of Overweight Normoglycemic Offspring of T2DM Parents and Non-Diabetic Parents

Background: The primary causes of Type 2 Diabetes Mellitus (T2DM) are largely unknown but insulin insensitivity has been reported to be a risk factor for the T2DM through the alteration of insulin sensitivity pattern. There is paucity of studies on the effect of exercise on occurrence of T2DM in offspring of diabetic parents in our population. Objectives: This study was designed to assess the effect of exercise on insulin sensitivity (IS) on offspring of T2DM parents compared with offspring of non-diabetic parents. Design: This study involved 60 offspring of T2DM parents attending University College Hospital, Ibadan and 60 offspring of non-diabetic parents who are undergraduate students of the University of Ibadan, Nigeria. Participants were randomly assigned into two groups. Each participant followed a protocol of graded exercise using ‘‘tummy trimmer’’ everyday spending 45 minutes daily for 24 weeks. Blood samples were obtained after an overnight fasting for determination of insulin sensitivity using standard methods at baseline and at 24 weeks. Data were analyzed using descriptive statistic and student t test with significance at p<0.05). Results: The most populated aged group was 26 to 35 years of which 47.3% (n=26) were OODP and 52.7% (n=29) were OONDP. However, all subjects were overweight with mean BMI of OODP and OONDP (29.30kg/m2±0.71 versus 26.37kg/m2±0.88) p=.0.035. Significantly, total insulin sensitivity between the two groups increased after 6 months of exercise p=0.045(3.36µ /l±0.24 versus 3.48µ /l±0.24). Conclusions: Male subjects tend to have higher insulin sensitivity than females.

Association of Serum Iron Indices with Insulin Resistance Index in Euglycaemic Offspring’s of Diabetic and Non Diabetic Parents: A Case-control Study

Introduction: Altered iron metabolism may be a risk factor for various diseases. There are studies showing that altered iron metabolism is frequently found in type 2 diabetes mellitus patients, but there is lacunae of literature in offspring’s of diabetic parents. Aim: To compare serum iron indices in euglycaemic offsprings of diabetic and non diabetic parents and also to correlate serum iron indices with HOMA-IR. Materials and Methods: This was a case-control study conducted in RL Jalappa Hospital and Research Centre, Kolar, Karnataka, India, from February 2019 to January 2020. Total 80 euglycaemic healthy individuals were recruited. Out of 80 subjects 40 were cases and 40 were controls. Offspring of non diabetic parents as control group and offspring of diabetic parents as a case group were included in the study. Anthropometric measurements like weight, height was measured and Body Mass Index (BMI) was calculated. Laboratory parameters like complete haemogram, Fasting Blood Sugar (FBS), serum iron markers like serum iron, serum ferritin, serum Total Iron Binding Capacity (TIBC), serum insulin and high sensitive C-reactive protein were analysed and compared between cases and controls. Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) was calculated. Results: Mean age of cases was 34.65±3.06 years and controls was 35.75±3.43 years respectively. Out of total 24 were females and 56 were males. Serum iron markers like serum iron and serum ferritin was significantly increased and serum TIBC was significantly decreased among euglycaemic offspring’s of diabetic parents compared to offspring’s of non diabetic parents. Serum ferritin (r-value=0.389,p-value=0.007) and serum iron (r-value=0.483,p-value=0.001), showed positive correlation with HOMA-IR among euglycaemic offspring’s of diabetic parents. On multiple regression analysis, in model 1 (HOMAIR as dependent variable and serum ferritin, serum iron and serum TIBC as independent variable) serum iron emerged as a significant predictor of insulin resistance, whereas after adding confounding variables like BMI, high-sensitivity C-Reactive Protein (hsCRP), lipid profile with serum iron markers in model 2, serum iron emerged as independent predictor of insulin resistance though regression equations was not statistically significant. Conclusion: Offsprings of diabetic parents showed iron overload and insulin resistance which predisposes them to develop T2DM and serum iron can be used as one of the marker of insulin resistance among offspring of diabetic parents along with other parameters.

334-OR: Sex Differences in Protein Phosphorylation in Insulin Resistance in Humans at the Cellular Level

Insulin resistance in muscle precedes and predicts type 2 diabetes in offspring of diabetic parents and is also observed in ~25% of the general population. However, whether these changes represent cell autonomous defects or are secondary to changes in circulating factors is unclear. To define possible cell autonomous determinants of insulin resistance, we have utilized induced pluripotent stem cell (iPSC) differentiated into myoblasts from 20 nondiabetic individuals - 10 insulin sensitive (I-Sen) and 10 insulin resistant (I-Res) as assessed using the steady-state plasma glucose approach. While there was no difference in the ability of the iPSCs to differentiate into myoblasts (iMyos), cells from I-Res individuals show impaired insulin signaling, decreased insulin-stimulated glucose uptake, and glycogen synthase activity compared to iMyos from insulin sensitive individuals, indicating that these cells mirror in vitro the alterations seen in vivo. The global phosphoproteomic analysis using LC-MS/MS uncovered a large network of proteins whose phosphorylation was altered in association with insulin resistance, mostly outside the canonical insulin-signaling cascade. We also observed striking differences in the phosphoproteomic signature of iMyos derived from male versus female subjects. Analysis of the proteins involved reveals that male cells show enhanced phosphorylation of proteins associated with transcription, Rho GTPases, SUMOylation, mRNA splicing, and membrane trafficking, whereas females show a dominance of phosphorylation of proteins involved in the cell cycle, chromatin organization, gene expression, and protein ubiquitination. Taken together, these data demonstrate major alterations in cellular signaling underlying insulin resistance, even in the absence of diabetes, and provide evidence of a super-network of cell signaling differences in males and females that must be considered in understanding cellular regulation in health and disease. Disclosure N. Haider: None. J. Lebastchi: None. T. M. Batista: None. H. Pan: None. J. Dreyfuss: None. I. Carcamo-orive: None. J. Knowles: None. C. Kahn: Advisory Panel; Self; ERX Pharmaceuticals, Kaleido Biosciences, Inc., Consultant; Self; Flagship Pioneering, Sana/Cobalt.

Heart rate variability as a tool for early diagnosis of autonomic neuropathy in non diabetic off springs of diabetic parents

Heart rate variability as a tool for early diagnosis of autonomic neuropathy in non diabetic off springs of diabetic parents

A study of heart rate variability among non-diabetic offspring of type 2 diabetic parents

Background: Type 2 diabetes mellitus is an inheritable condition that runs in families as a disorder of impaired glycemic control and its complications. Among the complications of diabetes, autonomic neuropathy contributes to the development of cardiovascular disease states besides diabetic vascular complications. Sympathovagal imbalance is reported to be observed among the non-diabetic first-degree relatives of diabetic population. Aims and Objectives: To assess the heart rate variability (HRV) parameters in non-diabetic normotensive offspring of diabetic parents and infer the impairment in sympathovagal balance in them by comparing with the HRV findings of non-diabetic offspring of non-diabetic parents. Materials and Methods: This cross-sectional observational study was conducted on 30 healthy non-diabetic, normotensive volunteers with parental history of Type 2 diabetes and 30 non-diabetic normotensive volunteers without parental history of diabetes. The volunteers were between the age of 17 and 25 years with normal body mass index and no health condition that could influence the cardiovascular health. The basal cardiovascular parameters and a 5 min lead II electrocardiogram for short-term HRV analysis were recorded to assess the sympathovagal balance. Results: The HRV analysis reveals a statistically significant increase in the sympathetic components and decreased parasympathetic components in the nondiabetic offspring of diabetic parents when compared to the non-diabetic offspring of non-diabetic parents. Conclusion: From our study, it could be observed that the non-diabetic offspring of diabetic parents have enhanced sympathetic activity and attenuated vagal activity even in their non-diabetic state, thus inferring an early onset of sympathovagal imbalance that could predispose them to hypertension and its sequel.

Assessment of regional body fat and body mass index with glycemic status in the middle-aged offspring of type 2 diabetic parents - A cross-sectional study

Background: Genetic predisposition is a key factor in developing insulin resistance in prone individuals. Sedentary lifestyle, lack of regular physical exercise, excessive intake of junk foods, and stress are proved to be important factor in the development of obesity. Assessing occurrence of insulin resistance earlier, an important component of metabolic syndrome can prevent the morbidity in the subjects. Aims and Objectives: This study aims to correlate body mass index (BMI), visceral fat, and subcutaneous fat individually with glycemic status of the subject and assess the better predictor of insulin resistance. Materials and Methods: Detailed questionnaire concerned with the study and informed consent was obtained from the subjects. The study included 100 middle-aged non-diabetic offspring of diabetic parents. The mean age of diabetic subjects was 39.4 years. Age - 35–45 years, subjects with BMI in the range between 18.5 and 30 kg/m2 were included in the study while diabetics, hypertensives, alcoholics, smokers, and subjects with any other recent illness were excluded from the study. Visceral fat and subcutaneous fat were measured using BC-601 TANITA bioimpedance analyzer. Fasting blood sugar was measured using single prick glucometer technique. Results: Pearson correlation was applied. Fasting blood sugar showed significant positive correlation with visceral fat and subcutaneous fat with r value of + 0.329 and + 0.464, respectively. Fasting blood sugar did not correlate with BMI and has an r value of + 0.050 only. Conclusion: Visceral fat and subcutaneous fat remain a better predictor than BMI in monitoring the preponderance to insulin resistance.

Correlation between BMI and Blood Pressure with Arterial Stiffness among Middle Aged Offspring of Diabetic Parents

Correlation between BMI and Blood Pressure with Arterial Stiffness among Middle Aged Offspring of Diabetic Parents

Association of Nutritional Status and Serum Leptin in Offsprings of Diabetic Parents of Karachi, Pakistan

Objective: Prevalence of diabetes in Pakistan in the year 2014 was 6.9 million and is expected to rise to approximately 13 million in 2035, ranking Pakistan at 8th position among world's top 10 countries having diabetes. Materials and Methods: The study design is young subjects were taken aged 18 to 24 and were classified according to their family history of type 2 diabetes mellitus (T2DM) into those with single diabetic parent (SDP), both diabetic parents (BDP) and subjects having no family history of diabetes (NDP). Body composition was assessed by measuring body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR). Fasting venous blood was analyzed for glucose and leptin levels (measured by immunoenzymetric assay). Results: The offspring of BDP had significantly higher body weight as compared to those of SDP and NDP (p<0.05). The mean fasting serum leptin levels among NDP, SDP and BDP were significantly different (p<0.05), and were respectively, 4.91±6.78, 15.55±13.49 and19.04 ±14.57 ng/mL. Conclusion: Hyperleptinemia and anthropometric indices are the most prominent indicators of T2DM in individuals with a history of diabetes in the family

Muscular Performance in Euglycemic off Springs of Diabetic Parents Using Mosso`s Ergograph

Muscular Performance in Euglycemic off Springs of Diabetic Parents Using Mosso`s Ergograph

A case-control study of cardiovascular parasympathetic function tests in offsprings of type 2 diabetes mellitus parents

Background: Type 2 diabetes mellitus (DM) has a strong genetic component. Individuals of a parent with type 2 DM have an increased (40%) risk of diabetes. If both parents have type 2 DM, the risk approaches to 70%. Thus, this study was designed to evaluate cardiovascular parasympathetic functions in offsprings of type 2 diabetic parents. Aims and Objectives: Study was done to compare and observe the degree of changes (if any) in the cardiovascular parasympathetic function tests in the offsprings of diabetic parents (cases) with offsprings of non-diabetic parents (controls) and provides timely lifestyle modifications to prevent the development of diabetes and its complications. Materials and Methods: The cardiovascular parasympathetic function tests were carried out in 50 healthy offsprings of type 2 diabetic parents (study group) and 50 healthy offsprings of non-diabetic parents (control group) in the age range of 18-25 years randomly selected medical and para-medical students. Statistical analysis was done by unpaired Student’s t-test. Results: Study shows decrease in all the three parasympathetic function tests (heart rate variability in response to deep breathing, heart rate variation in response to standing, and valsalva maneuver) in offsprings of type 2 diabetic parents (cases) as compared to non-diabetic parents (controls). However, the results were not statistically significant. Conclusion: Our observations indicate that genetic factors in the form of altered genes could pass from diabetic parents to their offsprings and could manifest as altered response in parasympathetic function tests in healthy offsprings of diabetic parents even before the offsprings developing diabetes.

Pattern Visual Evoked Potential in Non Diabetic offspring‘s of Type II Diabetes

Metabolic abnormalities in diabetes mellitus involves ganglionic and preganglionic elements in the entire retina and macular region causing visual disturbances. Subclinical central nervous system (CNS) dysfunctions have been reliably detected by visual evoked potentials in patients with uncomplicated diabetes and normal brain Computed tomography (CT) scan. The offspring of diabetic parents have a higher risk of diabetes and a possibility of diabetic retinopathy. The study aims at evaluating visual evoked potential in asymptomatic, non-diabetic offspring of diabetic parents. A total of 150 individuals in each group (case and controls) were enrolled after Written and informed consent. Institutional ethical Committee approval was obtained. Visual evoked potential (VEP) recordings were done using the standard procedure given in Recommended Standards for VEP, Guidelines 9B. The statistical analysis revealed significant difference in controls and offspring of diabetic parents in terms of P100 latency in both left and right eye (P&lt;0.05). The offspring of diabetic parents may be screened with VEP, as, prolongation of P100 latency a direct sign of retinal damage and demyelination could add the risk to the fact that they may be in a pre-diabetic stage without clinical manifestation, but there may be subclinical optic pathway involvement which mandates active intervention to reduce the co-morbidly associated with diabetes.

Maternal overweight and obesity are associated with increased risk of type 1 diabetes in offspring of parents without diabetes regardless of ethnicity.

The incidence of type 1 diabetes in children is increasing in Sweden, as is the prevalence of maternal overweight/obesity. Therefore, the aim of this study was to investigate if maternal overweight/obesity increases the risk of type 1 diabetes in offspring of parents with and without diabetes, and of different ethnicities. The study cohort comprised 1,263,358 children, born in Sweden between 1992 and 2004. Children were followed from birth until diagnosis of type 1 diabetes, emigration, death or end of follow-up in 2009, whichever occurred first. First trimester maternal BMI was calculated (kg/m(2)). Poisson regression was used to calculate incidence rate ratios (IRRs) with 95% CI for type 1 diabetes in the offspring. The risk of type 1 diabetes was increased in offspring of parents with any type of diabetes regardless of parental ethnicity. High first trimester maternal BMI was associated with increased risk of type 1 diabetes only in offspring of parents without diabetes (IRR 1.33 [95% CI 1.20, 1.48]). Increasing incidence of type 1 diabetes in children with non-diabetic parents may partly be explained by increasing prevalence of maternal overweight/obesity.

The Impact of the eNOS Glu298→Asp Polymorphisms on Endothelial and Diastolic Function in Non-Diabetic Offspring of Diabetic Parents

Objective: The aim of the present study was to investigate the relationship of the eNOS Glu298→Asp polymorphisms with impaired flow mediated dilatation (FMD) and diastolic dysfunction in Egyptian children with family history of type-2 diabetes Mellitus (DM). Materials and methods: Brachial artery FMD and echocardiographic study were performed in 80 (mean age, 11.5 ± 2.2 years) Egyptian non-diabetic offspring of patients with DM, and 80 (mean age, 10.6+2.4 years) Egyptian non-diabetic offspring of non-diabetic parents. Analysis of the endothelial nitric oxide synthase gene polymorphism using polymerase chain reaction and restriction fragment length polymorphism. for detection of different genotype variants (Glu/Glu (GG), Glu/Asp (GT) and Asp/Asp (TT) genotype). Results: Offspring of diabetic parents showed an increase in the frequency of Glu298Asp polymorphisms, significantly higher compared with controls (P<0.0001). The FMD% was significantly correlated with impaired diastolic dysfunction in offspring of diabetic patients (r=0.435 for IVRT and r=462 for E/Em). The Glu298Asp was significantly associated with impaired FMD and elevated E/Em among non-diabetic offspring of diabetic patients (P<0.001 and <0.005). Conclusion: Glu298Asp polymorphism in the endothelial nitric oxide synthase gene was significantly associated with impaired FMD and diastolic dysfunction in non-diabetic children with family history of diabetes.

Maternal overweight and obesity increase the risk of type 1 diabetes in offspring of parents without diabetes regardless of ethnicity

Maternal overweight and obesity increase the risk of type 1 diabetes in offspring of parents without diabetes regardless of ethnicity

LIPID Profile and Growth Indicators among Offspring’s of Diabetic Parents in Karachi, Pakistan

Background: Type 2 diabetes mellitus has become a universal problem. Globally 80% of lower and middle income countries are suffering from diabetes. Different studies show that offspring from diabetic parents growth indicators were disturbed the lipid profile and growth indicators. The objective of the study was to determine the levels of lipid profile and growth indicators among offspring of diabetic parents. Material and methods: Cross sectional study was done. Total 180 subjects were recruited from Dow university of Health sciences and classified as both parents were diabetic (BDP), Single Parents Diabetic (SDP) and no parents were diabetic (NDP). The Growth indicators lipid profile was measured. The analyst concentration of Lipids was analyzed by The Roche Hitachi Analyzer 902 Automated Analyzer automatically .Fasting blood sugar levels was determined by glucose oxidase. Results: Those offspring who gave history of diabetes in parents had their growth indicators and Lipid Profile were disturbed or raised when compared with non -diabetic parents. 25.6%, 5.6% and 5.6% of offspring belongs to Both Parents Diabetic (BDP), Single Diabetic Parents (SDP) and Not Diabetic Parents (NDP) respectively have obese. Similar lipid profile indicators also raised as More BDP and SDP subjects had high cholesterol (>200 mg/dL) than NDP (76.9% and 29.6% versus 10% respectively), More BDP and SDP subjects had high cholesterol (>150 mg/ dL) than NDP (23.1% and 2.8% versus 0% respectively). More BDP and SDP subjects had high cholesterol (>130 mg/dL) than NDP (76.9% and 29.6% versus 15% respectively). Conclusions: Lipid profiles of offspring were related to diabetic parent’s history. Early screening and change in lifestyle modification can be a preventive intervention for the risk of developing diabetes in future.

Serum Insulin and Insulin Resistance in the Off-Springs of Type 2 Diabetes Mellitus

Background: Type 2 diabetes mellitus has become a universal problem. Globally 80% of lower and middle income countries are suffering from diabetes. Aims: To determine the levels of serum insulin and to assess the insulin resistance in the offspring of diabetic parents as the predicting factors of Type 2 diabetes. Material and Methods: It is a cross-sectional study. The subjects were classified by their family history of T2DM; those with Single Diabetic Parent (SDP), Both Diabetic Parents (BDP) and No Diabetic Parents (NDP). Fasting blood sugar levels were determined by glucose oxidase and serum insulin by chemi luminescent immunometric assay. Insulin resistance was assessed by HOMA-IR index. Results: Fasting glucose was within normal range. Mean values for fasting serum Insulin levels of three groups of subjects though fell within the normal range but the levels both in SDP and BDP were significantly higher (P 0.05) than NDP . Conclusions: Hyperinsulinemia seems a predicting factor of T2DM in subjects who have a history of diabetes in parents.

A Bayesian population analysis of the development of type 2 diabetes in the offspring of diabetic parents

Disease progression of type 2 diabetes (T2D) has received considerable attention, but little is known about the disease development of T2D. The purposes of this study were to identify disease development variables (DDV) for development of T2D and to compare corresponding models for disease development. All subjects included in this study were the offspring of diabetic parents and were followed up to 25years. Repeated fasting blood samples were collected during the follow-up. Longitudinal data of four DDVs, namely fasting blood glucose (FBG), fasting serum insulin (FSI), homeostatic model assessment of insulin resistance (HOMA-IR) and body mass index (BMI) were recorded and compared. According to the diabetes status at the end of the follow-up, the data analysis involved a progressor group of 25 subjects, and a non-progressor group of 127 subjects. The temporal changes in the four DDVs over the time course of the disease development were evaluated by a single-slope and a dual-slope population-based Bayesian model. A dual-slope model based on FBG was found to be the best disease development model. For non-progressors, the FBG baseline stayed at 69.2 [66.5, 72.1]mg/dl (Bayes estimate [95% Bayesian credible set]) and increased with age by a rate of 0.227mg/dl [0.149, 0.3] per year. For the progressors, the FBG increase with age the same rate as non-progressors and started to have an additional increase of 2.27 [0.505, 4.52]mg/dl per year, starting 8.73 [-10.8, -6.93] years before the diagnosis of T2D. No significant longitudinal increasing or decreasing temporal pattern was found for FSI, HOMA-IR and BMI by the population-based Bayesian approach. The proposed model, which enables a quantitative, time-based evaluation of the development of T2D in this higher risk population, may be used to quantify the effect of interventions/prevention strategies such as drug treatment and lifestyle changes.

Association between parental history of diabetes and type 2 diabetes genetic risk scores in the PPP-Botnia and Framingham Offspring Studies

ObjectiveParental history of diabetes and specific gene variants are risk factors for type 2 diabetes, but the extent to which these factors are associated is unknown. MethodsWe examined the association between parental history of diabetes and a type 2 diabetes genetic risk score (GRS) in two cohort studies from Finland (population-based PPP-Botnia study) and the US (family-based Framingham Offspring Study). ResultsMean (95% CI) GRS increased from 16.8 (16.8–16.9) to 16.9 (16.8–17.1) to 17.1 (16.8–17.4) among PPP-Botnia participants with 0, 1, and 2 parents with diabetes, respectively (ptrend=0.03). The trend was similar among Framingham Offspring but was not statistically significant (p=0.07). The meta-analyzed p value for trend from the two studies was 0.005. ConclusionsThe very modest associations reported above suggest that the increased risk of diabetes in offspring of parents with diabetes is largely the result of shared environmental/lifestyle factors and/or hitherto unknown genetic factors.

Reduced insulin-mediated glucose uptake by euglycemic clamp in offspring of patients with type 2 diabetes.

Family studies point to an important genetic element in the genesis of type 2 diabetes. A variety of metabolic abnormalities have been documented in offspring of patients with type 2 diabetes. It has not been shown, however, at what age reduced insulin sensitivity is demonstrable using the sensitive the euglycemic clamp technique. To address this issue we screened 425 consecutive type 2 diabetic patients and examined all available (n = 48) normotensive, normoglycemic, non-smoking offspring (mean age 31.4+/-0.9 years) and compared them to 22 healthy offspring of non-diabetic parents (controls). The two groups were of similar age and BMI. Measurements in offspring and controls included baseline IRI, tissue glucose uptake (TGU, using euglycemic hyperinsulinemic clamp technique), and 24 hour ambulatory blood pressure (ABP). TGU was significantly (p < 0.001) lower in offspring of diabetic parents (338.8+/-19.9 (mol/kg/min) when compared to controls (516.6+/-22.2 micromol/kg/min). 24 h systolic ABP was significantly higher (p < 0.02) in propositi compared to controls (121.2+/-2.2 mm Hg and 113.8+/-1.7 mm Hg, respectively). No difference in triglycerides concentration was found. A borderline negative correlation was observed, however, between triglyceride levels and TGU (R = -0.48, p < 0.001). TGU was not related to the presence or absence of diabetic nephropathy in the parents. We conclude: Insulin resistance and various facets of the metabolic syndrome are demonstrable even at age 30 years in young non-obese, normotensive offspring of patients with type 2 diabetes. These disturbances are not related to the presence of microvascular complications in parents.