Prevention of insulin resistance in adolescents at risk for type 2 diabetes with depressive symptoms: 1-year follow-up of a randomized trial

Objectives. To evaluate body mass index standard deviation score (BMI-SDS), insulin sensitivity, and progression to type 2 diabetes mellitus (T2DM) in children at risk for T2DM approximately 3 years after being diagnosed with overweight/obesity and insulin resistance (measured by Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]). Methods. Out of 86 invited children, 44 (mean age 15.4 ± 3.6 years) participated. Medical history, physical examination, and laboratory workup were performed. Results. While the mean BMI-SDS significantly increased from 2.9 to 3.4, the mean HOMA-IR significantly decreased from 5.5 to 4.6 (baseline vs follow-up visit). Change in HOMA-IR was only due to a decrease in mean fasting plasma insulin (24.1 vs 21.1, P = .073). Conclusions. Although increase in BMI-SDS in these children is worrisome, the American Diabetes Association recommended screening interval of 3 years for children at risk for T2DM is not too long based on the fact that none of our study participants developed T2DM.

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Visceral Adiposity Index is associated with Insulin Resistance, impaired Insulin Secretion, and β-cell dysfunction in subjects at risk for Type 2 Diabetes

Diabetes Epidemiology and Management ◽

10.1016/j.deman.2021.100013 ◽

2021 ◽

pp. 100013

Author(s):

Froylan David Martínez-Sánchez ◽

Valerie Paola Vargas-Abonce ◽

Andrea Rocha-Haro ◽

Romina Flores-Cardenas ◽

Milagros Fernández-Barrio ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

At Risk ◽

Insulin Secretion ◽

Visceral Adiposity ◽

Visceral Adiposity Index ◽

Β Cell ◽

Cell Dysfunction ◽

Impaired Insulin

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Factors associated with the onset of major depressive disorder in adults with type 2 diabetes living in 12 different countries: results from the INTERPRET-DD prospective study

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796020000438 ◽

2020 ◽

Vol 29 ◽

Author(s):

C. E. Lloyd ◽

N. Sartorius ◽

H. U. Ahmed ◽

A. Alvarez ◽

S. Bahendeka ◽

...

Keyword(s):

Type 2 Diabetes ◽

Major Depressive Disorder ◽

Depressive Symptoms ◽

Depressive Disorder ◽

Life Events ◽

Stressful Life Events ◽

Regression Analyses ◽

Major Depressive

Abstract Aims To examine the factors that are associated with changes in depression in people with type 2 diabetes living in 12 different countries. Methods People with type 2 diabetes treated in out-patient settings aged 18–65 years underwent a psychiatric assessment to diagnose major depressive disorder (MDD) at baseline and follow-up. At both time points, participants completed the Patient Health Questionnaire (PHQ-9), the WHO five-item Well-being scale (WHO-5) and the Problem Areas in Diabetes (PAID) scale which measures diabetes-related distress. A composite stress score (CSS) (the occurrence of stressful life events and their reported degree of ‘upset’) between baseline and follow-up was calculated. Demographic data and medical record information were collected. Separate regression analyses were conducted with MDD and PHQ-9 scores as the dependent variables. Results In total, there were 7.4% (120) incident cases of MDD with 81.5% (1317) continuing to remain free of a diagnosis of MDD. Univariate analyses demonstrated that those with MDD were more likely to be female, less likely to be physically active, more likely to have diabetes complications at baseline and have higher CSS. Mean scores for the WHO-5, PAID and PHQ-9 were poorer in those with incident MDD compared with those who had never had a diagnosis of MDD. Regression analyses demonstrated that higher PHQ-9, lower WHO-5 scores and greater CSS were significant predictors of incident MDD. Significant predictors of PHQ-9 were baseline PHQ-9 score, WHO-5, PAID and CSS. Conclusion This study demonstrates the importance of psychosocial factors in addition to physiological variables in the development of depressive symptoms and incident MDD in people with type 2 diabetes. Stressful life events, depressive symptoms and diabetes-related distress all play a significant role which has implications for practice. A more holistic approach to care, which recognises the interplay of these psychosocial factors, may help to mitigate their impact on diabetes self-management as well as MDD, thus early screening and treatment for symptoms is recommended.

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Elevated circulating follistatin associates with an increased risk of type 2 diabetes

Nature Communications ◽

10.1038/s41467-021-26536-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Chuanyan Wu ◽

Yan Borné ◽

Rui Gao ◽

Maykel López Rodriguez ◽

William C. Roell ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

Genome Wide Association Study ◽

Regulatory Protein ◽

Alcoholic Fatty Liver ◽

Increased Risk

AbstractThe hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04–1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09–1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.

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Diagnosis and follow-up of type 2 diabetes in women with PCOS: a role for OGTT?

Acta Endocrinologica ◽

10.1530/eje-18-0237 ◽

2018 ◽

Vol 179 (3) ◽

pp. D1-D14 ◽

Cited By ~ 5

Author(s):

Marianne Andersen ◽

Dorte Glintborg

Keyword(s):

Type 2 Diabetes ◽

At Risk ◽

Glucose Tolerance ◽

Polycystic Ovary ◽

Normal Weight ◽

Oral Glucose ◽

Diagnostic Purpose ◽

Glycemic Status

Polycystic ovary syndrome (PCOS) is common in premenopausal women. The majority of women with PCOS have insulin resistance and the risk of type 2 diabetes mellitus (T2D) is higher in women with PCOS compared to controls. In non-pregnant women with PCOS, glycemic status may be assessed by oral glucose tolerance test (OGTT), fasting plasma glucose (FPG) or HbA1c. OGTT has been reckoned gold standard test for diagnosing T2D, but OGTT is rarely used for diagnostic purpose in other non-pregnant individuals at risk of T2D, apart from PCOS. OGTT has questionable reproducibility, and high sensitivity of the 2-h glucose value is at the expense of relatively low specificity, especially regarding impaired glucose tolerance (IGT). Furthermore, lean women with PCOS are rarely diagnosed with T2D and only few percent of normal-weight women have prediabetes. Glycemic status is necessary at diagnosis and during follow-up of PCOS, especially in women with high risk of T2D (obesity, previous gestational diabetes (GDM)). We suggest that OGTT should be used in the same situations in PCOS as in other patient groups at risk of T2D. OGTT is indicated for diagnosing GDM; however, OGTT during pregnancy may not be indicated in lean women with PCOS without other risk factors for GDM.

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Sustained Improvements in Glucose Metabolism Late After Roux-En-Y Gastric Bypass Surgery in Patients with and Without Preoperative Diabetes

Scientific Reports ◽

10.1038/s41598-019-51516-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Nils B. Jørgensen ◽

Kirstine N. Bojsen-Møller ◽

Carsten Dirksen ◽

Christoffer Martinussen ◽

Maria S. Svane ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Gastric Bypass ◽

Glucose Metabolism ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Relative Change

Abstract To describe glucose metabolism in the late, weight stable phase after Roux-en-Y Gastric Bypass (RYGB) in patients with and without preoperative type 2 diabetes we invited 55 RYGB-operated persons from two existing cohorts to participate in a late follow-up study. 44 (24 with normal glucose tolerance (NGT)/20 with type 2 diabetes (T2D) before surgery) accepted the invitation (median follow-up 2.7 [Range 2.2–5.0 years]). Subjects were examined during an oral glucose stimulus and results compared to preoperative and 1-year (1 y) post RYGB results. Glucose tolerance, insulin resistance, beta-cell function and incretin hormone secretion were evaluated. 1 y weight loss was maintained late after surgery. Glycemic control, insulin resistance, beta-cell function and GLP-1 remained improved late after surgery in both groups. In NGT subjects, nadir glucose decreased 1 y after RYGB, but did not change further. In T2D patients, relative change in weight from 1 y to late after RYGB correlated with relative change in fasting glucose and HbA1c, whereas relative changes in glucose-stimulated insulin release correlated inversely with relative changes in postprandial glucose excursions. In NGT subjects, relative changes in postprandial nadir glucose correlated with changes in beta-cell glucose sensitivity. Thus, effects of RYGB on weight and glucose metabolism are maintained late after surgery in patients with and without preoperative T2D. Weight loss and improved beta-cell function both contribute to maintenance of long-term glycemic control in patients with type 2 diabetes, and increased glucose stimulated insulin secretion may contribute to postprandial hypoglycemia in NGT subjects.

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Glycolysis/gluconeogenesis- and tricarboxylic acid cycle–related metabolites, Mediterranean diet, and type 2 diabetes

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa016 ◽

2020 ◽

Vol 111 (4) ◽

pp. 835-844 ◽

Cited By ~ 3

Author(s):

Marta Guasch-Ferré ◽

José L Santos ◽

Miguel A Martínez-González ◽

Clary B Clish ◽

Cristina Razquin ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Relative Risk ◽

Mediterranean Diet ◽

Tca Cycle ◽

Tricarboxylic Acid ◽

Model Assessment ◽

Weighted Score

ABSTRACT Background Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear. Objectives We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions. Methods We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were allocated to MedDiet + extra-virgin olive oil, MedDiet + nuts, or control diet. Plasma metabolites were measured using a targeted approach by LC–tandem MS. We tested the associations of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with subsequent T2D risk using weighted Cox regression models and adjusting for potential confounders. We designed a weighted score combining all these metabolites and applying the leave-one-out cross-validation approach. Results Baseline circulating concentrations of hexose monophosphate, pyruvate, lactate, alanine, glycerol-3 phosphate, and isocitrate were significantly associated with higher T2D risk (17–44% higher risk for each 1-SD increment). The weighted score including all metabolites was associated with a 30% (95% CI: 1.12, 1.51) higher relative risk of T2D for each 1-SD increment. Baseline lactate and alanine were associated with baseline and 1-y changes of homeostasis model assessment of insulin resistance. One-year increases in most metabolites and in the weighted score were associated with higher relative risk of T2D after 1 y of follow-up. Lower risks were observed in the MedDiet groups than in the control group although no significant interactions were found after adjusting for multiple comparisons. Conclusions We identified a panel of glycolysis/gluconeogenesis-related metabolites that was significantly associated with T2D risk in a Mediterranean population at high cardiovascular disease risk. A MedDiet could counteract the detrimental effects of these metabolites. This trial was registered at controlled-trials.com as ISRCTN35739639.

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Complement Factor 3 Is Associated With Insulin Resistance and With Incident Type 2 Diabetes Over a 7-Year Follow-up Period: The CODAM Study

Diabetes Care ◽

10.2337/dc13-2804 ◽

2014 ◽

Vol 37 (7) ◽

pp. 1900-1909 ◽

Cited By ~ 42

Author(s):

Nick Wlazlo ◽

Marleen M.J. van Greevenbroek ◽

Isabel Ferreira ◽

Edith J.M. Feskens ◽

Carla J.H. van der Kallen ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Complement Factor ◽

Incident Type ◽

Incident Type 2 Diabetes

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Clinical Measures of Physical Fitness Predict Insulin Resistance in People at Risk for Diabetes

Physical Therapy ◽

10.2522/ptj.20080064 ◽

2008 ◽

Vol 88 (11) ◽

pp. 1355-1364 ◽

Cited By ~ 31

Author(s):

Chiao-Nan Chen ◽

Lee-Ming Chuang ◽

Ying-Tai Wu

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Body Mass Index ◽

At Risk ◽

Risk Factor ◽

Waist Circumference ◽

Physical Fitness ◽

Clinical Measures

Background and Purpose Physical inactivity has been well documented as a risk factor for type 2 diabetes. Previous studies measured the level of physical activity either with questionnaires or with direct measurements of maximum oxygen uptake. However, questionnaires are patient-report measures, and methods for obtaining direct maximum oxygen uptake measurements often are not available clinically. The purpose of this study was to investigate whether clinical measurement of health-related physical fitness with a simple test battery can predict insulin resistance, a precursor of type 2 diabetes, in people at risk for diabetes. Subjects and Methods A total of 151 volunteers with at least one diabetes risk factor (overweight, hypertension, dyslipidemia, family history, impaired glucose tolerance, gestational diabetes, or delivering a baby weighing more than 4.0 kg) were recruited. Insulin resistance (as determined with the homeostasis model assessment of insulin resistance [HOMA-IR]), physical fitness (including body composition, as determined with the body mass index and waist circumference), muscle strength (handgrip strength [force-generating capacity]), muscle endurance (sit-up test), flexibility (sit-and-reach test), and cardiorespiratory endurance (step test) were measured, and a physical activity questionnaire was administered. Backward regression analysis was used to build the prediction models for insulin resistance from components of physical fitness and physical activity. Results Body mass index, muscle strength, and cardiorespiratory fitness predicted HOMA-IR in men (adjusted R2=.264). In women, age, waist circumference, and cardiorespiratory fitness were the predictors of HOMA-IR (adjusted R2=.438). Discussion and Conclusion Clinical measures of physical fitness can predict insulin resistance in people at risk for diabetes. The findings support the validity of clinical measures of physical fitness for predicting insulin resistance in people at risk for diabetes.

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