Lifetime congenital isolated GH deficiency does not protect from the development of diabetes

ObjectivesAdult subjects with untreated, lifetime, isolated GH deficiency (IGHD) due to a homozygous GHRH receptor gene mutation (MUT/MUT) residing in Itabaianinha, Brazil, present with lower BMI, higher prevalence of impaired glucose tolerance (IGT), increased insulin sensitivity (IS), and reduced β-cell function (βCF) when compared with non-BMI-matched homozygous normal controls. However, the prevalence of diabetes mellitus (DM) in this cohort is unknown. Comparing their IS and βCF with BMI-matched individuals heterozygous for the same mutation (MUT/N) may be useful to elucidate the role of the GH–IGF1 axis in IS and βCF. The purposes of this work were to verify the prevalence of IGT and DM in adult MUT/MUT subjects from this kindred and to compare IS and βCF in MUT/MUT and MUT/N.DesignCross-sectional study.MethodsWe studied most (51) of the living IGHD adults of this kindred who are GH naive. The oral glucose tolerance test (OGTT) could be performed in 34 subjects, fasting glucose was measured in 15, while two had a previous diagnosis of DM. The OGTT results of 24 MUT/MUT subjects were compared with those of 25 BMI-matched MUT/N subjects. IS was assessed by homeostatic model assessment of insulin resistance (HOMA–IR), quantitative IS check index, and oral glucose IS index for 2 and 3 h. βCF was assayed by HOMA-β, insulinogenic index, and the area under the curve of insulin:glucose ratio.ResultsThe prevalence of DM and IGT in IGHD was 15.68 and 38.23% respectively. IS was increased and βCF was reduced in MUT/MUT in comparison with MUT/N.ConclusionsLifetime, untreated IGHD increases IS, impairs βCF, and does not provide protection from diabetes.

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Impaired Insulin Action Is Associated With Increased Glucagon Concentrations in Nondiabetic Humans

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-01197 ◽

2017 ◽

Vol 103 (1) ◽

pp. 314-319 ◽

Cited By ~ 11

Author(s):

Anu Sharma ◽

Ron T Varghese ◽

Meera Shah ◽

Chiara Dalla Man ◽

Claudio Cobelli ◽

...

Keyword(s):

Glucose Tolerance ◽

Insulin Action ◽

Cell Function ◽

Medical Center ◽

Academic Medical Center ◽

Glucagon Secretion ◽

Tolerance Test ◽

Oral Glucose ◽

Cross Sectional ◽

Cell Dysfunction

Abstract Context Abnormal glucagon concentrations contribute to hyperglycemia, but the mechanisms of α-cell dysfunction in prediabetes are unclear. Objective We sought to determine the relative contributions of insulin secretion and action to α-cell dysfunction in nondiabetic participants across the spectrum of glucose tolerance. Design This was a cross-sectional study. A subset of participants (n = 120) was studied in the presence and absence of free fatty acid (FFA) elevation, achieved by infusion of Intralipid (Baxter Healthcare, Deerfield, IL) plus heparin, to cause insulin resistance. Setting An inpatient clinical research unit at an academic medical center. Participants A total of 310 nondiabetic persons participated in this study. Interventions Participants underwent a seven-sample oral glucose tolerance test. Subsequently, 120 participants were studied on two occasions. On one day, infusion of Intralipid plus heparin raised FFA. On the other day, participants received glycerol as a control. Main Outcome Measure(s) We examined the relationship of glucagon concentration with indices of insulin action after adjusting for the effects of age, sex, and weight. Subsequently, we sought to determine whether an acute decrease in insulin action, produced by FFA elevation, altered glucagon concentrations in nondiabetic participants. Results Fasting glucagon concentrations correlated positively with fasting insulin and C-peptide concentrations and inversely with insulin action. Fasting glucagon was not associated with any index of β-cell function in response to an oral challenge. As expected, FFA elevation decreased insulin action and also raised glucagon concentrations. Conclusions In nondiabetic participants, glucagon secretion was altered by changes in insulin action.

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Glycemic Predictors of Insulin Independence After Total Pancreatectomy With Islet Autotransplantation

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2016-2952 ◽

2016 ◽

Vol 102 (3) ◽

pp. 801-809 ◽

Cited By ~ 11

Author(s):

Michael Quartuccio ◽

Erica Hall ◽

Vikesh Singh ◽

Martin A. Makary ◽

Kenzo Hirose ◽

...

Keyword(s):

Glucose Tolerance ◽

Cell Function ◽

Fasting Glucose ◽

Total Pancreatectomy ◽

Area Under The Curve ◽

Johns Hopkins Hospital ◽

Oral Glucose ◽

Model Assessment ◽

Patient Counseling ◽

Insulin Independence

Abstract Context: Total pancreatectomy with islet auto transplantation (TPIAT) is a treatment for medically refractory chronic pancreatitis that can prevent postsurgical diabetes in some patients. Predictors of insulin independence are needed for appropriate patient selection and counseling. Objective: To explore glycemic predictors of insulin independence after TPIAT. Design: A prospective cohort of patients. Methods: We investigated 34 patients undergoing TPIAT from 2011-2016 at Johns Hopkins Hospital, all had a 75-g oral glucose tolerance test (OGTT) administered prior to their TPIAT. The primary outcome was insulin independence 1 year after TPIAT. Results: Ten of 34 (29%) patients were insulin independent 1 year after TPIAT. All patients with impaired fasting glucose and/or impaired glucose tolerance preoperatively were insulin dependent at 1 year. In age-adjusted regression analyses, fasting glucose ≤ 90 mg/dL [odds ratio (OR) = 6.56; 1.11 to 38.91; P = 0.04], 1-hour OGTT glucose ≤ 143 mg/dL (OR = 6.65; 1.11 to 39.91; P = 0.04), and 2-hour OGTT glucose ≤ 106 mg/dL (OR = 11.74; 1.46 to 94.14; P = 0.02) were significant predictors of insulin independence. In receiver operating characteristic analyses, homeostatic model assessment of β-cell function (HOMA-β) was the most robust predictor of insulin independence [area under the curve (AUC) = 0.88; 0.73 to 1.00]. Conclusions: Normal preoperative glucose status and lower fasting and postchallenge OGTT glucose values are significant predictors of insulin independence after TPIAT. Higher islet function (HOMA-β) was the strongest predictor. OGTT testing may be a useful tool to aid in patient counseling prior to TPIAT and should be further investigated.

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Decreased Circulating MANF in Women with PCOS is Elevated by Metformin Therapy and is Inversely Correlated with Insulin Resistance and Hyperandrogenism

Hormone and Metabolic Research ◽

10.1055/a-1082-1080 ◽

2020 ◽

Vol 52 (02) ◽

pp. 109-116

Author(s):

Jie Wei ◽

Cong Wang ◽

Gangyi Yang ◽

Yanjun Jia ◽

Yang Li ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Neurotrophic Factor ◽

Tolerance Test ◽

Oral Glucose ◽

Model Assessment ◽

Metformin Treatment ◽

Fat Percentage ◽

Cross Sectional ◽

Metformin Therapy

AbstractMesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel neurotrophic factor. Although recent studies have suggested that MANF appeared to be associated with insulin resistance, the results have been inconsistent. The aim of our study was to determine the serum MANF levels in women with PCOS and controls, to investigate their relationship to insulin resistance, and to evaluate circulating MANF changes with metformin intervention in PCOS women. We conducted a series of cross-sectional and interventional studies in 90 newly diagnosed patients with PCOS and 60 age- and gender-matched controls. Oral glucose tolerance test and euglycemic-hyperinsulinemic clamps were performed to assess the glucose tolerance and insulin sensitivity. Forty-three women with PCOS were randomly assigned to six months of oral metformin therapy. Serum MANF levels were significantly lower in women with PCOS than in controls. Serum MANF levels were positively correlated with M-value and negatively correlated with body mass index (BMI), body fat percentage (FAT), homeostatic model assessment of insulin resistance (HOMA-IR), and free androgen index (FAI). Multivariate stepwise regression demonstrated that serum MANF levels were independently associated with M-value and FAI. After six months of metformin treatment, there was a significant increase in serum MANF levels in PCOS women. Serum MANF levels are decreased in women with PCOS, and are reversely related to insulin resistance and hyperandrogenism. Metformin treatment elevates serum MANF levels and alleviates insulin resistance and hyperandrogenism in PCOS women.

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Serum apoA1 (Apolipoprotein A-1), Insulin Resistance, and the Risk of Gestational Diabetes Mellitus in Human Pregnancy—Brief Report

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.119.313195 ◽

2019 ◽

Vol 39 (10) ◽

pp. 2192-2197 ◽

Cited By ~ 2

Author(s):

Ravi Retnakaran ◽

Chang Ye ◽

Philip W. Connelly ◽

Anthony J. Hanley ◽

Mathew Sermer ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Cell Function ◽

Density Lipoprotein ◽

Tolerance Test ◽

Oral Glucose ◽

Model Assessment ◽

Human Pregnancy ◽

Matsuda Index ◽

Β Cell Function

Objective: apoA1 (apolipoprotein A-1) is the main lipoprotein associated with HDL (high-density lipoprotein) cholesterol. It was recently reported that intravenous infusion of apoA1 could lower insulin resistance in pregnant rats, leading to the suggestion that apoA1 could provide a target for reducing pregnancy-induced insulin resistance and the risk of gestational diabetes mellitus (GDM) in humans. However, the effects of apoA1 on insulin resistance and risk of GDM in human pregnancy are not known. Thus, we sought to systematically evaluate the relationships of apoA1 with glucose homeostasis and metabolic function in pregnant women. Approach and Results: In this study, 870 pregnant women were recruited in late second trimester and underwent metabolic characterization, including an oral glucose tolerance test on which 214 were diagnosed with GDM. Metabolic characterization included assessment of glucose tolerance, insulin sensitivity/resistance (Matsuda index, homeostasis model assessment of insulin resistance), pancreatic β-cell function, lipids (LDL [low-density lipoprotein] cholesterol, HDL cholesterol, triglycerides, apoB [apolipoprotein B], and apoA1), CRP (C-reactive protein), and adiponectin. Serum apoA1 was strongly correlated with HDL (r=0.79, P <0.0001) and weakly so with adiponectin (r=0.12, P =0.0004) but showed no association with measures of insulin sensitivity/resistance, β-cell function, glycemia, or CRP. There were no significant differences across apoA1 tertiles in mean adjusted Matsuda index ( P =0.24), homeostasis model assessment of insulin resistance ( P =0.08), or area under the glucose curve on the oral glucose tolerance test ( P =0.96). Moreover, there were no differences in risk of GDM across tertiles of apoA1, both before ( P =0.67) and after covariate adjustment ( P =0.78). Conclusions: Serum apoA1 is not associated with insulin resistance or the risk of GDM in human pregnancy.

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Higher circulating adiponectin and lower orosomucoid were associated with postload glucose ≤70 mg/dL, a possible inverse marker for dysglycemia, in young Japanese women

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2018-000596 ◽

2019 ◽

Vol 7 (1) ◽

pp. e000596 ◽

Cited By ~ 3

Author(s):

Ayaka Tsuboi ◽

Satomi Minato ◽

Megumu Yano ◽

Mika Takeuchi ◽

Kaori Kitaoka ◽

...

Keyword(s):

Glucose Tolerance ◽

Fat Mass ◽

Cell Function ◽

Serum Insulin ◽

Japanese Women ◽

Serum Adiponectin ◽

Oral Glucose ◽

Insulinogenic Index ◽

Model Assessment ◽

Central Adiposity

ObjectiveTo examine whether serum adiponectin and orosomucoid were associated with postload glucose ≤70 mg/dL during an oral glucose tolerance test (OGTT), termed as postload low glycemia, a possible inverse marker for dysglycemia.Research design and methods75 g OGTTs were performed with multiple postload glucose and insulin measurements over a 30–120 min period in 168 normal-weight Japanese women (18–24 years). Insulin resistance (IR) and β-cell function inferred from serum insulin kinetics during OGTT, fat mass and distribution by dual-energy X-ray absorptiometry (DXA), serum adiponectin and inflammatory markers were compared cross-sectionally between 39 women with and 129 women without postload low glycemia.ResultsOf 168 women, 161 had normal glucose tolerance. Women with as compared with those without postload low glycemia had lower fasting and postload glycemia despite similar fasting and postload insulinemia. They had higher insulinogenic index (p=0.03) and lower adipose IR (a product of fasting free fatty acid and insulin, p=0.01), although DXA-derived general and central adiposity, the Matsuda Index and homeostasis model assessment-IR did not differ. In addition, they had higher adiponectin and lower orosomucoid (both p<0.001). Multivariate logistic regression analyses revealed that adiponectin (OR: 1.14, 95% CI 1.03 to 1.26, p=0.009) and orosomucoid (0.96, 0.93 to 0.97, p=0.008) were associated with postload low glycemia independently of adipose IR and insulinogenic index.ConclusionsHigher adiponectin and lower orosomucoid were associated with 70 or lower mg/dL of postload glucose, a possible inverse marker for dysglycemia, in young women independently of DXA-derived fat mass and distribution, insulin secretion and IR.

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Four Plasma Glucose and Insulin Responses to a 75 g OGTT in Healthy Young Japanese Women

Journal of Diabetes Research ◽

10.1155/2018/5742497 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Kei Takahashi ◽

Hidetaka Nakamura ◽

Hiroshi Sato ◽

Hideto Matsuda ◽

Kazuo Takada ◽

...

Keyword(s):

Glucose Tolerance ◽

Plasma Glucose ◽

Area Under The Curve ◽

Tolerance Test ◽

Oral Glucose ◽

Peak Time ◽

Insulinogenic Index ◽

Late Type ◽

Physical Measurements ◽

Altered Glucose

The incidence of diabetes has been gradually increasing, not only in middle-aged individuals but also in young individuals. However, insulin and glucose patterns have not been investigated in apparently healthy young individuals, as they are typically grouped as controls. In this study, we investigated and classified glucose and insulin patterns in healthy young women. Sixty-two nonobese women without metabolic disease were recruited. The subjects underwent a 75 g oral glucose tolerance test (OGTT), physical measurements, and a biochemical examination. Two subjects displayed impaired glucose tolerance. The 62 subjects were categorized into four patterns by plasma glucose and insulin peak time during OGTT: normal type (n=39), insulin-late type (n=11), insulin- and glucose-late type (n=7), and insulin-very late type (n=5). OGTT glucose and insulin levels at all time points, insulinogenic index, HOMA-IR, and glucose area under the curve (AUC) significantly differed among the four groups. However, insulin AUC did not significantly differ. We did not detect significant differences in body condition or biochemical measurements. Our study demonstrated that some healthy young individuals might have delayed insulin secretion by OGTT. Early detection of altered glucose metabolism might be helpful to improve lifestyle choices and prevent progression to diabetes.

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Measurement and Correlation of Indices of Insulin Resistance in Patients on Peritoneal Dialysis

Peritoneal Dialysis International ◽

10.3747/pdi.2013.00296 ◽

2016 ◽

Vol 36 (4) ◽

pp. 433-441 ◽

Cited By ~ 5

Author(s):

Kelli R. King-Morris ◽

Serpil Muge Deger ◽

Adriana M. Hung ◽

Phyllis Ann Egbert ◽

Charles D. Ellis ◽

...

Keyword(s):

Insulin Resistance ◽

Peritoneal Dialysis ◽

Glucose Tolerance ◽

Large Scale ◽

Tolerance Test ◽

Glucose Disposal ◽

Maintenance Hemodialysis ◽

Oral Glucose ◽

Model Assessment ◽

Cross Sectional

BackgroundInsulin resistance (IR) is common in maintenance dialysis patients and is associated with excess mortality. Hyperinsulinemic euglycemic glucose clamp (HEGC) is the gold standard for measuring IR. There are limited studies using HEGC for comparison to other indirect indices of IR in peritoneal dialysis (PD) patients, nor have there been direct comparisons between patients receiving PD and those on maintenance hemodialysis (MHD) with regard to severity of IR, methods of measurement, or factors associated with the development of IR.MethodsThis is a cross-sectional, single-center study performed in 10 prevalent PD patients of median age 48 years (range 41 – 54); 50% were female and 60% were African American. Insulin resistance was assessed by HEGC (glucose disposal rate [GDR]), homeostatic model assessment of IR (HOMA-IR), HOMA-IR corrected by adiponectin (HOMA-AD), leptin adiponectin ratio (LAR), quantitative insulin sensitivity check index (QUICKI), McAuley's index, and oral glucose tolerance test (OGTT) at each time point for a total of 18 studies. Retrospective analysis compared this cohort to 12 hemodialysis patients who had previously undergone similar testing.ResultsThe median GDR was 6.4 mg/kg/min (interquartile range [IQR] 6.0, 7.8) in the PD cohort compared with the MHD group, which was 5.7 mg/kg/min (IQR 4.3, 6.6). For both the PD and MHD cohorts, the best predictors of GDR by HEGC after adjusting for age, gender, and body mass index (BMI), were HOMA-AD (PD: r = -0.69, p = 0.01; MHD: r = -0.78, p = 0.03) and LAR (PD: r = -0.68, p < 0.001; MHD: r = -0.65, p = 0.04). In both groups, HOMA-IR and QUICKI failed to have strong predictive value. Eight of 10 PD patients had at least 1 abnormal OGTT, demonstrating impaired glucose tolerance.ConclusionsInsulin resistance is highly prevalent in PD patients. The adipokine based formulas, HOMA-AD and LAR, correlated well in both the PD and MHD populations in predicting GDR by HEGC, outperforming HOMA-IR. The use of these novel markers could be considered for large-scale, epidemiological outcome studies.

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