Effect of Parental Type 2 Diabetes on Offspring With Type 1 Diabetes

Thorn, Lena M.; Forsblom, Carol; Wadén, Johan; Söderlund, Jenny; Rosengård-Bärlund, Milla; Saraheimo, Markku; Heikkilä, Outi; Hietala, Kustaa; Pettersson-Fernholm, Kim; Ilonen, Jorma; Groop, Per‐Henrik

doi:10.2337/dc08-0472

Cited by 30 publications

(44 citation statements)

References 26 publications

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“…Specifically, we showed that subjects in the DCCT with parents with T2DM gained more weight with INT, had higher waist circumferences and insulin doses, and had lipid levels consistent with MetS. 12 These findings were confirmed in an independent cohort of patients with T1DM 32 and shown to be predictive of CAD in another observational cohort. 33 In the present analysis, increasing prevalence of individual family histories of diabetes, hypertension, and hyperlipidemia in DCCT were associated with increased IMT with INT during EDIC.…”

Section: Discussionmentioning

confidence: 60%

The Effect of Excess Weight Gain With Intensive Diabetes Mellitus Treatment on Cardiovascular Disease Risk Factors and Atherosclerosis in Type 1 Diabetes Mellitus

2013

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Rationale Intensive diabetes therapy of type 1 diabetes (T1DM) reduces diabetes complications but can be associated with excess weight gain, central obesity, and dyslipidemia. Objective The purpose of this study was to determine if excessive weight gain with diabetes therapy of T1DM is prospectively associated with atherosclerotic disease. Methods and Results Subjects with T1DM (97% Caucasian, 45% female, mean age 35 years) randomly assigned to intensive (INT) or conventional (CONV) diabetes treatment during the Diabetes Control and Complications Trial (DCCT) underwent intima-media thickness (IMT) (n=1015) and coronary artery calcium (CAC) score (n=925) measurements during follow-up in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. INT subjects were classified by quartile of BMI change during the DCCT. Excess gainers (4th quartile, including CONV subjects meeting this threshold) maintained greater BMI and waist circumference (WC), needed more insulin, had greater IMT (+5%, P<0.001 EDIC year 1, P=0.003 EDIC year 6), and trended towards greater CAC scores (OR 1.55, CI 0.97 – 2.49, P=0.07) than minimal gainers. DCCT subjects meeting metabolic syndrome criteria for WC and blood pressure had greater IMT in both EDIC years (P =0.02 to <0.001); those meeting HDL criteria had greater CAC scores (OR 1.6 and CI 1.1 – 2.4, P=0.01) during follow-up. Increasing frequency of a family history of diabetes, hypertension, and hyperlipidemia was associated with greater IMT thickness with INT but not CONV. Conclusions Excess weight gain in DCCT is associated with sustained increases in central obesity, insulin resistance, dyslipidemia and blood pressure, as well as more extensive atherosclerosis during EDIC.

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Section: Discussionmentioning

confidence: 60%

The Effect of Excess Weight Gain With Intensive Diabetes Mellitus Treatment on Cardiovascular Disease Risk Factors and Atherosclerosis in Type 1 Diabetes Mellitus

2013

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“…Because our main objective was to examine the effects of exposure of offspring to maternal diabetes during gestation, the focus was on the presence or absence of diabetes rather than type. Correct ascertainment of parental dysglycemia is supported both by prior studies demonstrating validity of diabetes history by questionnaire (7,19) and by the fact that birth weights of offspring from mothers with diabetes during pregnancy were increased as expected. Future studies that would distinguish the effects on offspring according to parental diabetes type would be of interest.…”

Section: Discussionmentioning

confidence: 83%

Relationship Between Parental Diabetes and Presentation of Metabolic and Glycemic Function in Youth With Type 2 Diabetes: Baseline Findings From the TODAY Trial

et al. 2015

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OBJECTIVEChildren whose parents have diabetes are at increased risk for developing type 2 diabetes. This report assessed relationships between parental diabetes status and baseline demographics, anthropometrics, metabolic measurements, insulin sensitivity, and β-cell function in children recently diagnosed with type 2 diabetes.RESEARCH DESIGN AND METHODSThe sample included 632 youth (aged 10–17 years) diagnosed with type 2 diabetes for <2 years who participated in the TODAY clinical trial. Medical history data were collected at baseline by self-report from parents and family members. Youth baseline measurements included an oral glucose tolerance test and other measures collected by trained study staff.RESULTSYouth exposed to maternal diabetes during pregnancy (whether the mother was diagnosed with diabetes prior to pregnancy or had gestational diabetes mellitus) were diagnosed at younger ages (by 0.6 years on average), had greater dysglycemia at baseline (HbA1c increased by 0.3% [3.4 mmol/mol]), and had reduced β-cell function compared with those not exposed (C-peptide index 0.063 vs. 0.092). The effect of maternal diabetes on β-cell function was observed in non-Hispanic blacks and Hispanics but not whites. Relationships with paternal diabetes status were minimal.CONCLUSIONSMaternal diabetes prior to or during pregnancy was associated with poorer glycemic control and β-cell function overall but particularly in non-Hispanic black and Hispanic youth, supporting the hypothesis that fetal exposure to aberrant metabolism may have long-term effects. More targeted research is needed to understand whether the impact of maternal diabetes is modified by racial/ethnic factors or whether the pathway to youth-onset type 2 diabetes differs by race/ethnicity.

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“…A small number of articles (n = 7) were also excluded for various reasons, including studies that were restricted to the enrolment of participants with genetic susceptibility to type 1 diabetes (human leukocyte antigen [HLA]), studies in which the outcome was islet autoimmunity rather than T1DM, a study that only reported the risk of DM, a study in which the onset of T1DM was not reported, or one study that had overlap of the patient population with another included study . Finally, 21 articles were eligible for the final inclusion in the present meta‐analysis. Of these, 12 were case‐control studies, eight were cohort studies, and one was a cross sectional study .…”

Section: Resultsmentioning

confidence: 99%

“…Finally, 21 articles were eligible for the final inclusion in the present meta‐analysis. Of these, 12 were case‐control studies, eight were cohort studies, and one was a cross sectional study . The characteristics of the included studies are summarized in Tables S1 ‐ S3.…”

Section: Resultsmentioning

confidence: 99%

The influence of maternal body mass index, maternal diabetes mellitus, and maternal smoking during pregnancy on the risk of childhood‐onset type 1 diabetes mellitus in the offspring: Systematic review and meta‐analysis of observational studies

2019

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Summary There is emerging evidence that events occurring before and shortly after birth may be important in determining the risk of childhood‐onset type 1 diabetes mellitus (T1DM). We aimed to summarize and synthesize the associations between maternal body mass index (BMI), maternal diabetes mellitus (DM), and maternal smoking during pregnancy and the risk of childhood‐onset T1DM in the offspring by performing a systematic review and meta‐analysis of observational studies. A random effects model was used to generate the summary risk estimates. The PubMed and Web of Science databases were searched to identify relevant observational studies. Twenty one observational studies were included in the present meta‐analysis. Compared with offspring of mothers with normal weight, offspring of women with overweight or obesity were at an increased risk of developing childhood‐onset T1DM (overweight: relative risk [RR] 1.09, 95% confidence interval [CI], 1.03‐1.15; obesity: RR 1.25, 95% CI, 1.16‐1.34; per 5 kg m−2 increase in BMI: RR 1.10, 95% CI, 1.06‐1.13). No association was found for maternal underweight (RR 0.92, 95% CI, 0.75‐1.13). Maternal DM was associated with an increased risk of childhood‐onset T1DM (RR 3.26, 95% CI, 2.84‐3.74). Regarding the type of maternal DM, the greatest risk of T1DM in the offspring appeared to be conferred by maternal T1DM (RR 4.46, 95% CI, 2.89‐6.89), followed by maternal gestational diabetes mellitus (RR 1.66, 95% CI, 1.16‐2.36), and lastly by maternal type 2 diabetes mellitus (RR 1.11, 95% CI, 0.69‐1.80). Additional analysis of studies comparing maternal versus paternal T1DM within the same population revealed that offspring of fathers with T1DM had a 1.5 times higher risk of developing childhood‐onset T1DM than offspring of mothers with T1DM (RR 9.58, 95% CI, 6.33‐14.48 vs. RR 6.24, 95% CI, 5.52‐7.07). Furthermore, a reduced risk of childhood‐onset T1DM was observed in infants born to mothers who smoked during pregnancy compared with infants born to mothers who did not smoke during pregnancy (RR 0.79, 95% CI, 0.71‐0.87). In summary, our findings add further evidence that early‐life events or environmental factors may play a role in modulating infants' risk of developing T1DM later in life.

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Effect of Parental Type 2 Diabetes on Offspring With Type 1 Diabetes

Cited by 30 publications

References 26 publications

The Effect of Excess Weight Gain With Intensive Diabetes Mellitus Treatment on Cardiovascular Disease Risk Factors and Atherosclerosis in Type 1 Diabetes Mellitus

The Effect of Excess Weight Gain With Intensive Diabetes Mellitus Treatment on Cardiovascular Disease Risk Factors and Atherosclerosis in Type 1 Diabetes Mellitus

Relationship Between Parental Diabetes and Presentation of Metabolic and Glycemic Function in Youth With Type 2 Diabetes: Baseline Findings From the TODAY Trial

The influence of maternal body mass index, maternal diabetes mellitus, and maternal smoking during pregnancy on the risk of childhood‐onset type 1 diabetes mellitus in the offspring: Systematic review and meta‐analysis of observational studies

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