Relatives Of Diabetic Patients Research Articles

Efficacy of DiaLife, an education program for relatives of adult patients with diabetes \u2013 study protocol of a cluster randomized controlled trial

BackgroundThe global prevalence of diabetes mellitus (DM) has been increasing over recent decades. In Germany, the prevalence for DM type 1 and type 2 in adults is estimated at about 7.7%. Hence, diabetes has to be classified as a serious public health concern. Being diagnosed with DM and facing possible sequelae might have a negative impact on patients’ mental and physical well-being. However, diabetes not only affects patients themselves, but also their close relatives. To improve the quality of life for patients and relatives alike, the German Association of Diabetes Nurses and Education experts (VDBD) elaborated the first education program tailor-made for relatives of diabetes patients. This article describes the concept and design of the trial evaluating the efficacy of this education program called “DiaLife—Living Together with Diabetes”.MethodsThis evaluation study is a cluster randomized controlled trial, in which the study centers will be randomly assigned either to the intervention group or the control group. Study centers will recruit relatives of and patients with DM type 1 and type 2. Members of the intervention group will participate in the education program DiaLife, whereas participants randomized in the control group will act as waiting-list controls. The study will assess the efficacy of DiaLife by comparing diabetes-related knowledge between the intervention and control groups as the primary outcome for participants. As the primary outcome in patients, the Hba1c value will be assessed. In addition, diabetes-related distress, family interaction, and other secondary endpoints will be considered as secondary outcomes. Long-term efficacy will be assessed 6 and 12 months after intervention. Hierarchical regression models will be used to analyze effects over time.DiscussionWhile there is scientific evidence for the efficacy of education programs addressed to (diabetes) patients, there is a research gap with regard to intervention studies evaluating the efficacy of education programs designed for patients’ relatives. The study results will provide information on the efficacy of the DiaLife education program. In addition, factors that might hinder a successful implementation of an education program for relatives will be identified.Trial registrationGerman Clinical Trials Register, DRKS00015157. Registered on 24 August 2018.

Predicting Diabetes in Relatives of Diabetic Patients Using Insulinoma Antigen-2 Antibody-A Biomarker for Type 1 Diabetes in Jos, Nigeria

Background: Type 1 diabetes is a chronic autoimmune disease caused by the destruction of insulin-secreting islet cells of the pancreas by several islet cell-specific autoantibodies that can be detected many months or years before the onset of diabetes. The presence of these antibodies can be attributed largely to environmental agents and also genetic factors. Knowing the frequency of these autoantibodies in a population is an important step for a better understanding, diagnosis and management of Type 1 diabetes. The aim of the research was to screen and identify those at greatest risk of diabetes (relatives of diabetic patients) early in life, as a precautionary step with the hope to deliver care in order to avoid the disease and its complications later in life. Method: The study was conducted on eighty-eight apparently healthy young and adolescent first-degree relatives of diabetic patients in Jos metropolis. Blood samples were collected, centrifuged and serum was aseptically separated within two hours. A commercial ELISA test kit - Medizym® anti-IA2 was used to determine the presence of anti-IA-2 autoantibodies in serum obtained from participants enrolled in the study. Results: The results obtained showed twelve participants of both sexes (13.64%) having positive titers of the IA-2 antibodies which were statistically significant. Conclusion: From the results, we conclude that with significant titers of the IA-2 antibodies among young adolescents, there is the likelihood of them developing diabetes later in life depending on the period of exposure to the factors responsible for triggering the autoimmune process. The results are hereby discussed and recommendations made.

Effect of oral insulin on prevention of diabetes in relatives of patients with T1DM: a randomized clinical trial

Insulin is one of the autoantigens involved in the pathogenesis of T1DM. Therefore several trials with insulin given orally, nasal or subcutaneous have been conducted to prevent the development of T1DM in genetically high risk populations. This trial design built on the results of DPT-1 and included further investigations related to first phase insulin release. A dose of 7.5 mg/d did not prevent T1DM in the high risk population of autoantibody positive T1DM relatives. Possibly ongoing trials with higher insulin doses might show better effects on beta cell autoimmunity and T1DM incidence. Knowledge of pre-diabetes staging has informed several prevention trials and epidemiological studies in high risk populations. Individuals with two or more beta cell antibodies are now classified as Stage 1. Without intervention, most of these will develop abnormal glucose tolerance (Stage 2) and then clinically manifest T1DM (Stage 3). The overall rate of progression from Stage 1 to 3 is ~9.5% per year.

Effect of Oral Insulin on Prevention of Diabetes in Relatives of Patients With Type 1 Diabetes

Type 1 diabetes requires major lifestyle changes and carries increased morbidity and mortality. Prevention or delay of diabetes would have major clinical effect. To determine whether oral insulin delays onset of type 1 diabetes in autoantibody-positive relatives of patients with type 1 diabetes. Between March 2, 2007, and December 21, 2015, relatives with at least 2 autoantibodies, including insulin autoantibodies and normal glucose tolerance, were enrolled in Canada, the United States, Australia, New Zealand, the United Kingdom, Italy, Sweden, Finland, and Germany. The main study group (n = 389) had first-phase insulin release on an intravenous glucose tolerance test that was higher than the threshold. The 55 patients in the secondary stratum 1 had an identical antibody profile as the main study group except they had first-phase insulin release that was lower than the threshold. Secondary strata 2 (n = 114) and strata 3 (n = 3) had different autoantibody profiles and first-phase insulin release threshold combinations. Follow-up continued through December 31, 2016. Randomization to receive 7.5 mg/d of oral insulin (n = 283) or placebo (n = 277), including participants in the main study group who received oral insulin (n = 203) or placebo (n = 186). The primary outcome was time to diabetes in the main study group. Significance was based on a 1-sided threshold of .05, and 1-sided 95% CIs are reported. Of a total of 560 randomized participants (median enrollment age, 8.2 years; interquartile range [IQR], 5.7-12.1 years; 170 boys [60%]; 90.7% white non-Hispanic; 57.6% with a sibling with type 1 diabetes), 550 completed the trial including 389 participants (median age, 8.4 years; 245 boys [63%]), 382 (96%) in the main study group. During a median follow-up of 2.7 years (IQR, 1.5-4.6 years) in the main study group, diabetes was diagnosed in 58 participants (28.5%) in the oral insulin group and 62 (33%) in the placebo group. Time to diabetes was not significantly different between the 2 groups (hazard ratio [HR], 0.87; 95% CI, 0-1.2; P = .21). In secondary stratum 1 (n = 55), diabetes was diagnosed in 13 participants (48.1%) in the oral insulin group and in 19 participants (70.3%) in the placebo group. The time to diabetes was significantly longer with oral insulin (HR, 0.45; 95% CI, 0-0.82; P = .006). The HR for time to diabetes for the between-group comparisons for the 116 participants in the other secondary stratum was 1.03 (95% CI, 0-2.11; P = .53) and for the entire cohort of 560 participants was 0.83 (95% CI, 0-1.07; P = .11), which were not significantly different. The most common adverse event was infection (n = 254), with 134 events in the oral insulin group and 120 events in the placebo group, but no significant study-related adverse events occurred. Among autoantibody-positive relatives of patients with type 1 diabetes, oral insulin at a dose of 7.5 mg/d, compared with placebo, did not delay or prevent the development of type 1 diabetes over 2.7 years. These findings do not support oral insulin as used in this study for diabetes prevention. clinicaltrials.gov Identifier: NCT00419562.

Area under the curve during OGTT in first-degree relatives of diabetic patients as an efficient indicator of future risk of type 2 diabetes and prediabetes.

To establish whether the area under the curve of an OGTT has a predictive role in identifying prediabetic and diabetic subjects among first-degree relatives (FDR) of patients with diabetes mellitus type 2 (DM). In a population-based cohort study, 766 FDR of diabetic patients with a normal glucose tolerance test (NGT) completed a 2-hour OGTT. They were followed up for 7years and classified according to the American Diabetes Association criteria into: NGT, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and DM. Relative risk (RR) and 95% confidence intervals (95%CI) were calculated based on logistic regression. Receiver operator characteristic (ROC) analysis along with AUC at different intervals and at time points during the OGTT was used to evaluate the risk of prediabetes and diabetes. Twenty-three subjects (3%) developed type 2 DM, 118 (29.3%) IFG, 81 (11.5%) IGT and 544 (71%) subjects remained NGT. AUC and mean difference of glucose in all high-risk groups demonstrated significant differences in both intervals and time points when compared to the NGT group. The cut-off values during OGTT to predict prediabetes and diabetes was determined as blood glucose more than 7.2 and 7.8mmol/L at 30 and 60minutes, respectively. The time point 60 has the highest predictive role for the development of diabetes, alone, and improved the performance of a prediction model containing multiple important clinical risk factors. The data suggest that the glycaemic response to an OGTT may predict the risk of development of diabetes in first-degree relatives of DM patients.

Heart rate variability in nondiabetic dyslipidemic young Saudi adult offspring of type 2 diabetic patients

Background: Autonomic imbalance has been described in first-degree relatives of diabetic patients, and dyslipidemia has been reported to induce sympathovagal imbalance (SVI). Aims and Objective: To assess the contribution of dyslipidemia to SVI in adults with positive family history of type 2 diabetes mellitus (T2DM). Materials and Methods: This is a cross-sectional study involving 150 male Saudi adults aged 19–30 years, recruited from students of College of Applied Medical Sciences in Taif University, Taif, Saudi Arabia. Lipid profile, atherogenic index (AI), body mass index (BMI), waist circumference (WC), basal heart rate (BHR), blood pressure (BP), spectral indices of heart rate variability (HRV), and homeostatic model of insulin resistance (HOMA-IR) were measured and analyzed in study groups (control subjects with no family history of T2DM, n = 50; positive family history of T2DM, nondyslipidemic subjects, n = 50 and dyslipidemic subjects n = 50). Result: In the dyslipidemic group, lipid profile, LF-HF (ratio of low-frequency to high-frequency power of HRV, a precise indicator of SVI) was significantly increased (P˂ 0.05) when compared with non dyslipidemic and the control groups. Increased SVI was owing to simultaneous sympathetic motivation and vagal inhibition. LF-HF ratio was positively correlated with the WC, SBP, DBP, BHR, total cholesterol (TC), low-density lipoprotein (LDL) and AI. Significant contribution of WC, DBP, BHR, TC, and AI to the LF-HF ratio in the dyslipidemic group was observed by multiple regression analysis. Conclusion: SVI in dyslipidemic subjects with family history of T2DM occurs owing to sympathetic activation and vagal depression. Dyslipidemia contributes to the SVI in these subjects.

Diabetes screening in the high risk individuals: Can the Glycosylated hemoglobin test replace oral glucose tolerance test?

Introduction First degree relatives of patients with type 2 diabetes carry a high risk of pre-diabetes and diabetes. We aimed to study the diagnostic accuracy of glycosylated hemoglobin test (HbA1c) and fasting blood glucose (FBS) in screening diabetes and pre-diabetes in this category. Methods 157 previously non-diabetic, adult, first degree relatives of diabetic patients underwent FBS, HbA1c and oral glucose tolerance test (OGTT). Sensitivity and specificity of FBS over 101 and 126 mg/ dL and HbA1c of 5.5% and 6.5% in detecting individuals with pre- diabetes and diabetes were determined according to the 2-hour OGTT blood glucose values of 140 and 200 mg /dL respectively. Results Majority (63%) of the sample were females. Mean (SD) age, BMI were 49.9(11) years and 23.5 (3.6) kg/m2. Percentages with diabetes on FBS, HbA1C and OGTT were 10.19%, 12.73%, 14% and pre-diabetes were 28.6%, 45.9% 30.57% respectively. Sensitivity and specificity of HbA1c in detecting pre-diabetes were 83.33% and 70.64% and diabetes were 77.27% and 97.77% respectively. The corresponding figures for pre-diabetes with FBS were 60.41% and 85.32% and diabetes 68.13% and 99.25%. Area under the curve of the receiver operator characteristic curves (ROC) of FBS and HbA1c with OGTT were 0.88 and 0.98 respectively. Conclusions In this high diabetes risk category, HbA1c test detects higher percentage of patients with diabetes and pre-diabetes than FBS. Diagnostic yield of diabetes with HbA1c was superior to FBS and almost identical to OGTT. HbA1c test may replace OGTT in detecting diabetes among high risk individuals.

Early detection of diabetes mellitus in high-risk children

ObjectiveThe aim of this study was to determine the value of glycosylated hemoglobin (HbA1c) as an early diagnostic marker for diabetes mellitus in high-risk groups such as relatives of diabetic patients (siblings) and obese children.BackgroundDiabetes mellitus is a chronic illness that requires continuing medical care and ongoing patient self-management education and support to prevent acute complications and reduce the risk of long-term complications.Patients and methodsThis study was conducted on 60 children attending the Genetic and Endocrine Unit of the Pediatric Department, Faculty of Medicine, Menoufia University.They were divided into two groups: group I [45 children who were relatives of diabetic patients (siblings)] and group II (15 obese children).The studied groups were subjected to detailed history taking, thorough clinical examination, anthropometric measurements, investigations (routine and special investigations through the estimation of HbA1c), and family counseling.ResultsAt the start, five (8.3%) children were in prediabetic stage (HbA1c level ranging between 5.7 and 6.4%); of them, two (4.4%) were relatives of diabetic patients and three (20%) children were from the obese group. At the end of the 3-month follow-up, with proper family counseling, a child from among the relatives of diabetic patients (2.2%) and another from the obese group (6.7%) were seen to have HbA1c within the normal range. At the end of 6 months of follow-up, one (6.7%) obese female patient was still in prediabetic stage.ConclusionThe HbA1c test is an early detector of diabetes mellitus among high-risk groups. Prediabetes occurs because of the interaction between genetic and environmental factors. Controlling the environmental factors by proper family counseling can delay and even inhibit the emergence of diabetes.

The effect of Dehydroepiandrosterone on insulin resistance in patients with impaired glucose tolerance

Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone-sulfate (DHEA-S) are the most abundant steroid hormones in the body. Recently, DHEA-S has gained interest as an antidepressant substance, with positive effects on autoimmune disease such as lupus and ulcerative colitis, as well as obesity, cancer, cardiovascular disease and diabetes. Its effect on insulin resistance is also assumed to be positive, but has not as yet been confirmed. The present cross-over clinical trial was conducted to evaluate the efficacy of DHEA and placebo on insulin resistance. Participants were selected among relatives of diabetic patients who were referred to the Isfahan Endocrine Research Center because of Impaired Glucose Tolerance (IGT) test. Thirty IGT patients were treated randomly with DHEA (50 mg/day) or placebo by cross-over clinical trial for six months and insulin resistance between the beginning and the end of each three months treatment period was assessed. At the end of the first three months, the mean changes from baseline of the various parameters in the drug group were: DHEA-S, 2.5 µmol/l (p=0.008); Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), 0.6 (p=0.6); insulin, 7.1 pmol/l (p=0.3) and FPG, 0.5 mmol/l (p=0.1). The changes in the placebo group were: DHEA-S, 0.08 µmol/l (p=0.6); HOMA-IR, 0.9 (p=0.03); FPG, 0.8 mmol/l (p=0.1); insulin, 25.1 pmol/l (p=0.05). In the second three months, the mean changes in the drug group were: DHEA-S, 4.5 µmol/l (p=0.003); Fasting Plasma Glucose (FPG), 0.1 mmol/l (p = 0.4); insulin, 4.3 pmol/l (p=0.2); HOMA-IR, 0.3 (p=0.1) and the changes in placebo group were: DHEA-S, 0.7 µmol/l (p=0.5); FPG, 0.3 mmol/l (p=0.3); insulin, 10.7 pmol/l (p=0.1); HOMA-IR, 0.6 (p=0.03). DHEA did not reduce insulin resistance, although there was a tendency to improvement. The data indicate a possible but not clearly favorable effect of DHEA on insulin resistance.

P194 “PARAOXONASE (PON1) GLN, ARG 192 POLYMORPHISM” AN INDEPENDENT RISK FACTOR FOR CORONARY ARTERY DISEASE IN NORTH-WEST INDIAN POPULATION

The activities of FAD-linked glycerophosphate dehydrogenase (m-GDH), glutamate dehydrogenase (G1DH), glutamate-pyruvate transaminase (GPT) and glutamate-oxalacetate transaminase (GOT) were measured in purified populations of CD3 + lymphocytes from 55 control subjects, 62 type-2 diabetics and 50 non-diabetic relatives of the latter patients. The activity of m-GDH was measured by both a radioisotopic procedure and colourimetric technique. As judged from these measurements and relative to the paired value for G1DH, the incidence of abnormally low m-GDH activity was significantly higher in type-2 diabetics than in control subjects. Moreover, the paired ratio in reaction velocity between the colourimetric and radioisotopic assay of m-GDH was abnormally high in patients with low m-GDH activity. Low m-GDH activity often coincided with increased GPT activity in plasma or high GPTGOT ratio in lymphocytes. No obvious clustering of these anomalies was found in relatives of diabetic patients. These findings suggest that an inherited or acquired genomic defect of m-GDH in lymphocytes, and possibly in pancreatic B-cells, may participate to the pathogenesis of non-insulin-dependent diabetes mellitus.

O cuidado à pessoa diabética e as repercussões na família

Esse estudo teve como objetivo compreender as repercussões na família da assistência oferecida após implementação de um programa educativo em diabetes. Entrevistamos seis familiares de pacientes diabéticos de um centro universitário de Ribeirão Preto-SP, em 2007. A análise temática dos dados possibilitou identificar três temas: familiares reconhecem que o Centro constitui um diferencial para adesão ao plano alimentar, atividade física e medicamentos; o Centro é reconhecido como espaço educativo para convívio e controle do diabetes; o paciente como elemento que multiplica e expande o conhecimento acerca do diabetes na família. Os resultados apontam que o programa educativo repercutiu favoravelmente na família, ampliando seu repertório de conhecimentos sobre o tratamento. O apoio do núcleo familiar é fundamental na adesão ao tratamento.

Introduction: The Use of Endophenotypes to Deconstruct and Understand the Genetic Architecture, Neurobiology, and Guide Future Treatments of The Group of Schizophrenias

This issue of Schizophrenia Bulletin includes a series of articles on the “endophenotype strategy” to explore and understand the genetics of “schizophrenia.” Initially, an atheoretical search for associations between the qualitative diagnostic disorder schizophrenia and regions of the genome was a useful first step in the high-risk voyage of discovery seeking genes conveying vulnerability to schizophrenia. However, with a huge ocean of 3 000 000 000 base pairs harboring 25 000 or so structural genes in Homo sapiens, alternative strategies for schizophrenia vulnerability gene identification were and are needed. In this issue, “Endophenotyping Schizophrenia” is an article that describes this alternative and rational endophenotype approach to gene discovery in schizophrenia. In 1972, Gottesman and Shields introduced the concept of the “endophenotype” into the schizophrenia literature to signify quantitative measures that were “intermediate,” functionally important links in the pathways between genetic variation and clinical expression of the disorder. Invisible to the naked eye and based on instrument or laboratory measurements, these heritable endophenotypes accounted, in principle, for genetic risk factors that interacted with nongenetic factors to create the brain-based neurobiological soil from which schizophrenia is more likely to spring forth. Gur et al and Turetsky et al describe some of these neurocognitive and neurophysiological endophenotypes that act as genetically mediated neurobiological components of the risk for developing schizophrenia. Schork et al show how advances in statistical genetics enable psychiatric geneticists and neuroscientists to use this endophenotypic information in the service of interrogating the genome and identifying specific genes and SNPs that create risk for developing schizophrenia. The advantages of the endophenotype strategy are that endophenotypes are quantitative and functionally relevant reflections of genetic risk, and they are amenable to advanced statistical analysis. Further, they increase the power of any subsequent analyses because more relatives will have the candidate endophenotype than will have the full-blown clinical phenotype of schizophrenia. A classical example in medicine is the role of an abnormal glucose tolerance test in the relatives of diabetes patients in furthering our understanding of the genetic architecture of diabetes itself. But exactly how can we get endophenotype information about families? Using endophenotype selection described by Braff et al and illustrated by Gur et al and Turetsky et al, this issue describes a model National Institute of Mental Health-funded project that uses a family-based, multisite endophenotype strategy to ascertain and gather information to unlock the genetic complexities of schizophrenia. In “The Consortium on the Genetics of Endophenotypes in Schizophrenia (COGS): Model Recruitment, Assessment, and Endophenotyping Methods for a Multi-Site Collaboration” by Calkins et al, the major issues and strategies for setting up the Consortium on the Genetics of Schizophrenia (COGS) are described. From training research assistants to reliably diagnosing schizophrenia to testing for quantitative endophenotypes, this article is an excellent guide to setting up and running a multisite consortium that explores the intricate genetic architecture of a complex multifactorial disorder such as schizophrenia. It should serve as a useful reference for others who are facing similar consortium-building challenges. The genesis and progress of the endophenotype strategy and its implementation in the COGS is well described in these articles. By starting with heritable and quantitative measures, cutting-edge statistical genetic analyses can be employed in order to unravel the complex genetic mysteries of schizophrenia. Certainly, as we utilize the genetic mantra of “DNA to RNA to Protein,” we must better understand genetic variation in the context of quantitative functional shifts in behavior, neurophysiology, metabolism, and neurodevelopment, which is complicated even further by epistasis (gene by gene interaction), gene by environment interaction, and by still unspecified epigenetic factors. The endophenotype strategy, although still in its infancy and open to challenge for some of its assumptions, potentially provides a very potent platform from which we can position ourselves to understand the genetics of schizophrenia and, ultimately, to select strong-inference–based compounds to treat or even prevent this cruel and devastating “no fault” clinical brain disorder. In addition, we could not have a series of articles on the endophenotype strategy without thanking Dr Gottesman for his ongoing, stimulating, and lively intellectual leadership in this field of psychiatric genetics and neuroscience. Speaking for all the COGS investigators, I hope that the reader gains knowledge, direction, and insight from these carefully crafted articles.

Glucose Intolerance, Insulin Resistance and Cardiovascular Risk Factors in First Degree Relatives of Women With Polycystic Ovary Syndrome

Findings on familial aggregation of polycystic ovary syndrome (PCOS) are consistent with a genetic component. Studies have shown greater insulin resistance (IR), higher serum androgen levels, more frequent glucose tolerance disorder, and more type II diabetes in first-degree relatives of patients with PCOS. The present study examined these variables in addition to cardiovascular risk factors in 120 family members of 55 patients with PCOS. There were 40 mothers, 38 fathers, 25 sisters, and 17 brothers. The control group included 75 healthy subjects with no family history of PCOS or diabetes. The study and control groups were matched for age and body weight. Insulin resistance was estimated by homeostatic model assessment (HOMA IR), log HOMA, insulin sensitivity index, the quantitative insulin sensitivity check index (QUICKI), and the area under the curve for insulin (AUCI) during an oral glucose tolerance test. Glucose intolerance of any degree was documented in 40% of mothers and 52% of fathers of patients with PCOS. Six cases of glucose tolerance disorder were found in control mothers and fathers (15%). First-degree relatives of patients with PCOS, compared with control subjects, had significantly higher serum levels of fasting insulin, HOMA-IR, log HOMA, and AUCI. Control subjects had significantly increased QUCKI, ISI levels. In addition, serum levels of adiponectin were significantly higher than in all subgroups of relatives of PCOS subjects. Fathers and mothers of patients with PCOS, but not brothers or sisters, had higher serum homocysteine and resistin levels. Blood lipid levels, including total cholesterol and low-density lipoprotein (LDL)-cholesterol, were significantly higher in fathers of patients with PCOS than in the control group. The opposite was the case for serum levels of high-density lipoprotein (HDL)-cholesterol and apoprotein A. Levels of total cholesterol, LDL-cholesterol, apoprotein B, and triglycerides were higher in mothers of patients with PCOS than in control subjects, but levels of HDL-cholesterol and apoprotein A were similar. Levels of most blood lipids were similar in patients' sisters than in control subjects, but brothers of patients had higher blood lipid levels than control subjects (exceptions were HDL-cholesterol and apoprotein A). Both groups of parents of patients with PCOS had higher blood pressure, but this was not true for the brothers and sisters. These findings indicate that first-degree relatives of patients with PCOS, like the patients themselves, are at increased risk of developing cardiovascular disease (CVD). These family members should be monitored for both CVD and diabetes, and preventive measures should be taken when appropriate.

Endothelial Dysfunction Precedes Arterial Stiffening in Normotensive Normoglycemic First Degree Relatives of Diabetic Patients

Endothelial Dysfunction Precedes Arterial Stiffening in Normotensive Normoglycemic First Degree Relatives of Diabetic Patients

Familiality of metabolic abnormalities is dependent on age at onset and phenotype of the type 2 diabetic proband.

To determine the impact of a family history of the common form of type 2 diabetes and the phenotype of the proband on anthropometric and metabolic variables in normoglycemic first-degree relatives, we studied 2,100 first-degree relatives of patients with the common form of type 2 diabetes (FH+) and 388 subjects without a family history of diabetes (FH-). All subjects participated in an oral glucose tolerance test to allow measurement of insulin secretion [30-min incremental insulin/glucose (I/G 30)] and insulin sensitivity [homeostasis model assessment (HOMA) of insulin resistance (IR)]. A subset participated in a euglycemic clamp (n = 75) and an intravenous glucose tolerance test (n = 300). To study the effect of a particular phenotype of the proband, insulin secretion and sensitivity were also compared between first-degree relatives of diabetic probands with high and low waist-to-hip ratio (WHR) and probands with early and late onset of diabetes. FH+ subjects were more insulin resistant, as seen from a higher HOMA-IR index (P = 0.006) and a lower rate of insulin-stimulated glucose uptake (P = 0.001) and had more features of the metabolic syndrome (P = 0.02, P = 0.0002) compared with FH- subjects. Insulin secretion adjusted for insulin resistance (disposition index, DI) was also lower in the FH+ vs. FH- subjects (P = 0.04). Relatives of diabetic probands with a high WHR had reduced insulin-mediated glucose uptake compared with relatives of probands with a low WHR (P = 0.04). Relatives of diabetic patients with age at onset <44 yr had higher HOMA IR (P < 0.005) and lower DI (P < 0.005) than relatives of patients with age at onset >65 yr (highest quartile). We conclude that early age at onset of type 2 diabetes and abdominal obesity have a significant influence on the metabolic phenotype in the nondiabetic first-degree relative.

In Pursuit of Type 1 Diabetes Prevention

Diabetes Prevention Trial–Type 1 Diabetes Study Group: Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 346:1685– 1691, 2002. [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Objective. To determine whether insulin can prevent or delay the onset of overt type 1 diabetes in relatives of patients with type 1 diabetes who are at increased risk of the disease. Design and methods. The Diabetes Prevention Trial–Type 1 (DPT-1) was a randomized, controlled, open comparison trial of prophylactic intervention with parenteral insulin versus no treatment in prediabetic subjects. First- and second-degree relatives of type 1 diabetic patients were recruited and screened with a test for islet cell antibodies (ICAs). Those who tested positive for ICAs were then staged to define their risk for diabetes by measuring insulin autoantibodies (IAAs), assessing oral glucose tolerance, and measuring first-phase insulin response to intravenous glucose. Researchers also screened for the presence of the haplotype known to be protective against diabetes (HLA-DQA1* 0102, DQB1*0602). Its presence excluded individuals from further participation. ICA-positive relatives were eligible for the parenteral trial if their first-phase insulin response was below a set threshold, if their oral glucose tolerance test (OGTT) results were not completely normal, or both. Such individuals have a 5-year projected risk of diabetes of more than 50%. Relatives who tested positive for ICAs and IAAs with normal glucose tolerance and a first-phase insulin response above the set threshold have intermediate risk for diabetes (5-year projected risk of 25–50%). These individuals were offered enrollment in the oral insulin trial, which is ongoing. The high-risk subjects were randomly assigned to either the experimental intervention (parenteral insulin) or to … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DDiabetes%2BPrevention%2BTrial-Type%2B1%2BDiabetes%2BStudy%2BGr%26rft.auinit1%253D%2B%26rft.volume%253D346%26rft.issue%253D22%26rft.spage%253D1685%26rft.epage%253D1691%26rft.atitle%253DEffects%2Bof%2BInsulin%2Bin%2BRelatives%2Bof%2BPatients%2Bwith%2BType%2B1%2BDiabetes%2BMellitus%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa012350%26rft_id%253Dinfo%253Apmid%252F12037147%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa012350&link_type=DOI [3]: /lookup/external-ref?access_num=12037147&link_type=MED&atom=%2Fdiaclin%2F20%2F4%2F168.atom [4]: /lookup/external-ref?access_num=000175834100002&link_type=ISI

Apolipoprotein E polymorphism as a cardiovascular risk factor in first-degree relatives of diabetic patients: The Rancho Bernardo study, 1984–1987

Apolipoprotein E polymorphism as a cardiovascular risk factor in first-degree relatives of diabetic patients: The Rancho Bernardo study, 1984–1987

Prediction of type 1 diabetes in first-degree relatives of diabetic patients in Czech Republic

Prediction of type 1 diabetes in first-degree relatives of diabetic patients in Czech Republic

FAD-glycerophosphate dehydrogenase activity in lymphocytes of type-2 diabetic patients and their relatives

The activities of FAD-linked glycerophosphate dehydrogenase (m-GDH), glutamate dehydrogenase (G1DH), glutamate-pyruvate transaminase (GPT) and glutamate-oxalacetate transaminase (GOT) were measured in purified populations of CD3 + lymphocytes from 55 control subjects, 62 type-2 diabetics and 50 non-diabetic relatives of the latter patients. The activity of m-GDH was measured by both a radioisotopic procedure and colourimetric technique. As judged from these measurements and relative to the paired value for G1DH, the incidence of abnormally low m-GDH activity was significantly higher in type-2 diabetics than in control subjects. Moreover, the paired ratio in reaction velocity between the colourimetric and radioisotopic assay of m-GDH was abnormally high in patients with low m-GDH activity. Low m-GDH activity often coincided with increased GPT activity in plasma or high GPT GOT ratio in lymphocytes. No obvious clustering of these anomalies was found in relatives of diabetic patients. These findings suggest that an inherited or acquired genomic defect of m-GDH in lymphocytes, and possibly in pancreatic B-cells, may participate to the pathogenesis of non-insulin-dependent diabetes mellitus.

Increased risk for type I (insulin-dependent) diabetes in relatives of patients with alopecia areata (AA).

The prevalence of various chronic diseases was compared in 517 individuals with alopecia areata, and 2,969 of their first degree relatives. As previous reports have suggested an increased incidence of diabetes in relatives of patients with alopecia areata, special attention was given to the prevalence of Type 1 and Type 2 diabetes in the patients and in their relatives. Several immunologic diseases were increased in alopecia probands and relatives. Thyroid disease, vitiligo, Addison disease, and pernicious anemia were more prevalent in probands and in their relatives than in the general population. Specifically, a high rate of thyroid disease was found in probands (14.7%) and in their first degree relatives (4.2%). Only one proband had Type 1 diabetes, yet there were 14 sibs with Type 1 diabetes. Thus, Type 1 diabetes was significantly more prevalent in the sibs (1.2%) than in either the probands with alopecia (0.2%), or the general population (0.12-0.25%) (P < 0.05)). In contrast, Type 2 diabetes was not more common in probands or in sibs than in the general population. These data suggest that alopecia areata protects against Type 1 diabetes in predisposed individuals. The high rate of thyroid disease suggests that screening probands and first degree relatives for thyroid disease should be considered.