The Diabetes Risk Phenotype of Young Women With Recent Gestational Diabetes

Rottenkolber, Marietta; Ferrari, Uta; Holland, L; Aertsen, Stephanie; Kammer, Nora N.; Hetterich, Holger; Fugmann, M; Banning, Friederike; Weise, M.; Sacco, Vanessa; Kohn, Denise; Freibothe, Ines; Hutter, Stefan; Hasbargen, Uwe; Lehmann, Rainer; Grallert, Harald; Parhofer, Klaus G.; Seißler, Jochen; Lechner, Andreas

doi:10.1210/jc.2014-3898

Cited by 45 publications

(61 citation statements)

References 32 publications

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“…Surprisingly, however, high plasma leptin levels often coexist with insulin resistance in human subjects. We and other groups have even found a negative correlation between fasting plasma leptin and insulin sensitivity after adjustment for BMI [4, 5]. Given the insulin-sensitizing effect of leptin, this finding requires dysfunction or saturation of leptin signaling, phenomena often summarized under the term “leptin resistance”.…”

Section: Introductionmentioning

confidence: 71%

“…Anthropometric data included body mass, body fat mass (determined by bioelectrical impedance analysis (Tanita BC-418; Tanita Corporation) [21, 22]), height, waist and hip circumference. A detailed description of the study design, anthropometric and clinical measurements as well as methodologies of blood sampling and analysis can be found elsewhere [4]. …”

Section: Methodsmentioning

confidence: 99%

“…Three days before MRI study, participants were advised to refrain from heavy exercise. The MRI study protocol has been described previously [4]. …”

Section: Methodsmentioning

confidence: 99%

“…It is a strong risk marker for subsequent type 2 diabetes mellitus (T2D) [2, 3], and women with recent GDM already show many metabolic characteristics associated with T2D [4]. …”

Section: Introductionmentioning

confidence: 99%

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Physical fitness and plasma leptin in women with recent gestational diabetes

et al. 2017

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Aims/HypothesisLow physical fitness (PF) is a risk factor for type 2 diabetes mellitus (T2D). Women with a history of gestational diabetes (GDM) are at risk for T2D at a young age, but the role of PF in this population is not clear. PF has also been found to correlate inversely with plasma leptin in previous studies. Here, we examine whether women who had GDM have lower PF than women after a normoglycemic pregnancy and, second, whether PF is associated with plasma leptin, independently of body fat mass.MethodsCross-sectional analysis of 236 participants in the PPSDiab Study (cohort study of women 3–16 months after delivery, 152 after gestational diabetes (pGDM), 84 after normoglycemic pregnancy (control subjects); consecutively recruited 2011–16); medical history, physical examination with bioelectrical impedance analysis (BIA), whole body magnetic resonance imaging (MRI) (n = 154), 5-point oral glucose tolerance test, cardiopulmonary exercise testing, clinical chemistry including fasting plasma leptin; statistical analysis with Mann–Whitney U and t -test, Spearman correlation coefficient, multiple linear regression.ResultsWomen pGDM had lower maximally achieved oxygen uptake (VO2peak/kg: 25.7(21.3–29.9) vs. 30.0(26.6–34.1)ml/min/kg; total VO2peak: 1733(1552–2005) vs. 1970(1767–2238)ml/min; p<0.0001 for both), and maximum workload (122.5(105.5–136.5) vs. 141.0(128.5–159.5)W; p<0.0001). Fasting plasma leptin correlated inversely with PF (VO2peak/kg ρ = -0.72 p<0.0001; VO2peak ρ = -0.16 p = 0.015; max. load ρ = -0.35 p<0.0001). These associations remained significant with adjustment for body mass index, or for body fat mass (BIA and MRI).Conclusions/InterpretationWomen with a recent history of GDM were less fit than control subjects. Low PF may therefore contribute to the risk for T2D after GDM. This should be tested in intervention studies. Low PF also associated with increased leptin levels–independently of body fat. PF may therefore influence leptin levels and signaling. This hypothesis requires further investigation.

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Section: Introductionmentioning

confidence: 71%

Section: Methodsmentioning

confidence: 99%

“…Three days before MRI study, participants were advised to refrain from heavy exercise. The MRI study protocol has been described previously [4]. …”

Section: Methodsmentioning

confidence: 99%

“…It is a strong risk marker for subsequent type 2 diabetes mellitus (T2D) [2, 3], and women with recent GDM already show many metabolic characteristics associated with T2D [4]. …”

Section: Introductionmentioning

confidence: 99%

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Physical fitness and plasma leptin in women with recent gestational diabetes

et al. 2017

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“…This case suggests that a GLP-1 receptor agonist may be a useful component of glucose-lowering therapy in individuals FIGURE 1 (a) Insulin sensitivity (M-value), as determined by the euglycaemic-hyperinsulinaemic clamp, of the familial partial lipodystrophy case (triangle) and 12 control participants [circles + boxplot; age-matched women with normoglycaemia (mean age: 34.4 years)] in the PPSDiab study [5]. (b) Insulin secretory response to a 0.3 g/kg body weight intravenous glucose bolus in the reported case (solid line) and the 12 control participants (dashed line + boxplots).…”

Section: Discussionmentioning

confidence: 99%

Insulin secretory defect in familial partial lipodystrophy Type 2 and successful long-term treatment with a glucagon-like peptide 1 receptor agonist

et al. 2017

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Background Familial partial lipodystrophies are rare monogenic disorders that are often associated with diabetes. In such cases, it can be difficult to achieve glycaemic control.Case report We report a 34-year old woman with familial partial lipodystrophy type 2 (Dunnigan) and diabetes; her hyperglycaemia persisted despite metformin treatment. A combined intravenous glucose tolerance-euglycaemic clamp test showed severe insulin resistance, as expected, but also showed strongly diminished first-phase insulin secretion. After the latter finding, we added the glucagon-like peptide-1 receptor agonist liraglutide to the patient's treatment regimen, which rapidly normalized plasma glucose levels. HbA 1c values <42 mmol/mol (6.0%) have now been maintained for over 4 years.Conclusion This case suggests that a glucagon-like peptide-1 receptor agonist may be a useful component of glucoselowering therapy in individuals with familial partial lipodystrophy and diabetes mellitus.

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