Compare Insulin Sensitivity Research Articles

Insulin Sensitivity, Islet Cell Function, and Incretin Axis in Pregnant Women With and Without Gestational Diabetes Mellitus.

The aim of this study was to compare insulin sensitivity, islet cell function, and incretin axes in pregnant subjects with GDM and normal healthy controls. Pregnant women at 24 to 28 weeks of gestation were subjected to a 75 g oral glucose tolerance test (OGTT). Samples for glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were collected at 0, 30, 60, and 120 min during the OGTT. The Matsuda index (MI) and insulin secretion and sensitivity index-2 (ISSI-2) were assessed. The glucagon suppression index (GSI) was calculated along with the area under the curve (AUC) for glucose, insulin, glucagon, GLP-1, and GIP. A total of 48 pregnant women (25 GDM and 23 controls) were finally analysed. The MI and ISSI-2 were low in the GDM group [4.31 vs. 5.42; P = 0.04], [1.99 vs. 3.18, P ≤ 0.01] respectively). Total AUCglucagon was higher in the GDM group (7411.7 vs. 6320.1, P = 0.02). GSI30 was significantly lower in the GDM group (-62.6 vs. -24.7, P = 0.03). Fasting GLP-1 levels were low in GDM women (17.3 vs. 22.2, P = 0.04). The total AUCGLP-1 positively correlated with total GSI in the GDM group. Asian-Indian GDM women have high insulin insensitivity, islet cell dysfunction, and low fasting GLP-1. Incretin axis dysfunction plays a potential role in their islet cell dysfunction.

Methionine Restriction Increases Insulin Sensitivity in Type-2 Diabetes via miRNA Activation

Methionine Restriction (MR) causes a higher level of circulating and hepatic fibroblastic growth factor 21 (FGF21). This leads to metabolic phenotypes, including increased energy expenditure, insulin sensitivity, and extended lifespan. Previous studies on obese mice have concluded that dietary MR in a high-fat regimen prevents hyperglycemia and improves glucose homeostasis, thus preventing type-2 diabetes, a multifactorial metabolic disease characterized by high blood glucose levels and cell insulin resistance. Recent experiments have shown that cells’ response to dietary MR includes changes in methylation of DNA promoters that activate or repress microRNAs (miRNAs), which are small endogenous nucleotide sequences and contain 18-22 base pairs that control gene expression for lipid metabolism. Considering that the disruption of miRNA levels affects insulin resistance, miRNA potentially plays a role in MR to increase insulin sensitivity for type-2 diabetes. In this paper, we investigate the mechanism of MR influencing the expression level of miRNA-15b to promote insulin sensitivity in obese organisms. Using our in-vitro model, we measured the expression of miRNA-15b in adipocytes cultured in MR and control conditions. Additionally, we compared insulin sensitivity and free fatty acid (FFA) metabolite levels between obese mice on control and MR diets. Taken together, we were able to verify the positive effects of MR in reducing hepatic fatty acid production, decreasing blood glucose levels, and increasing insulin sensitivity. However, miRNA-15b downregulates cells’ insulin signaling pathway and insulin sensitivity. Therefore, we proposed potential influences of MR on other miRNAs in reducing lipid cell differentiation and enhancing insulin sensitivity for future investigation.

A Cross-Sectional Multicentre Study to Validate Insulin Sensitivity Index Cut-Offs for Detection of Metabolic Syndrome in Indian Adolescents with Type-1 Diabetes.

A previous study compared insulin sensitivity indices for the detection of double diabetes (DD) in Indian adolescents with type-1 diabetes (T1D) and derived a cut-off to predict future risk for the development of metabolic syndrome (MS) in adolescents with T1D. We conducted the current study with the aim to validate these cut-offs for detecting DD among Indian subjects with T1D from various geographical locations. This multicentric cross-sectional study included 161 Indian adolescents with T1D. Demographic, anthropometric, clinical, and biochemical data were collected using standard protocols. Insulin sensitivity (IS) was calculated using various equations developed to determine insulin sensitivity in subjects with T1D. Metabolic syndrome was diagnosed using International Diabetes Federation (IDF) Consensus Definition 2017. We report 4.3% prevalence of MS in Indian adolescents with T1D with an additional 29.8% of study participants at risk of development of MS. Low High density lipoprotein (HDL) (23.6%) was the commonest abnormal component of the MS definition. Insulin sensitivity calculated by an equation derived by the SEARCH group was the most appropriate index to identify MS and metabolic risk in Indian adolescents with T1D. The proposed cut-off of 5.48 had high specificity, positive predictive value, and negative predictive value in identifying the risk of the development of DD. Insulin sensitivity calculated by the equation proposed by the SEARCH group together with cut-offs derived in earlier study may be used effectively to identify risk of development of MS/DD in Indian adolescents with T1D from various geographical locations.

Pyometra-associated insulin resistance assessment by insulin binding assay and tyrosine kinase activity evaluation in canine muscle tissue

Diestrus is associated with insulin resistance in bitches and pyometra can further impair insulin sensitivity. This study aimed to compare insulin sensitivity, insulin binding, and tyrosine kinase activity in bitches in anestrus, diestrus, or with pyometra. Patients submitted to elective ovariohysterectomy were divided into anestrus (n = 11) or diestrus (n = 13) according to reproductive history, vaginal cytology, and uterine histology. The group pyometra (n = 8) included bitches diagnosed with the disease based on clinical presentation and abdominal ultrasound findings and further confirmed by uterine histopathology. All patients were submitted to an intravenous glucose tolerance test (IVGTT) before ovariohysterectomy, and rectus abdominis muscle samples were collected during surgery for plasmatic membrane suspension preparation. Muscle-membranes were submitted to cold saturation insulin binding assay for dissociation constant (Kd) and maximum binding capacity (Bmax) determination, as well as exogenous substrate Poly (Glu: Tyr 4:1) phosphorylation assay for basal tyrosine kinase evaluation. Bitches with pyometra showed higher basal insulin (P < 0.001) and higher area under the curve (AUC) for insulin (P = 0.01) and glucose (P < 0.001) response during the IVGTT in comparison with bitches in anestrus or diestrus. Diestrus (P < 0.0001) and pyometra (P = 0.001) were associated with reduced tyrosine kinase activity in comparison with anestrus. No differences were documented in Kd and Bmax results for the low-affinity/high-capacity insulin receptors; however, high-affinity/low-capacity insulin receptors showed higher Kd and Bmax results in bitches in diestrus or with pyometra (P < 0.05) in comparison with anestrus. Despite the pyometra group showed the highest Kd values (P < 0.01), its Bmax results did not differ from the diestrus group (P > 0.05). Diestrus’ higher Kd values and reduced tyrosine kinase activity in muscle tissue were compensated by increased total insulin binding capacity. Absent differences in IVGTT results between diestrus and anestrus bitches corroborate this finding. However, in bitches with pyometra, the highest Kd values were not compensated by increased total insulin binding capacity. This finding was associated with insulin resistance and glucose intolerance in IVGTT results. Moreover, pyometra resolution restored insulin sensitivity and glucose tolerance. These features can play a key role in pyometra-associated CDM, as well as in diabetic remission after pyometra resolution.

1913-P: Differences in Glucose Absorption in African American (AA) Patients Presenting with DKA and Severe Hyperglycemia (SH)

Approximately 70% of obese AA patients with new-onset diabetes presenting with DKA and SH have near-normoglycemia remission with intensive insulin treatment. In addition to improvements in insulin secretion and/or sensitivity as potential mechanisms of remission, we hypothesize that gut glucose absorption may be associated with remission. To estimate gut glucose absorption, we developed a novel mathematical model that simultaneously estimates SI and gut glucose half-life (GIGt1/2, inversely related to glucose absorption). This study aimed to compare insulin sensitivity estimates of the novel model to estimates from Dalla Man’s OGTT model and also assess GIGt1/2. We included 42 AA patients who presented with new-onset DKA (n= 17) and SH (n=25). All subjects had a 75-gm 2-hour OGTT 1 week after insulin remission (REM) or at 3 months after continuous insulin therapy (no-REM). We estimated insulin sensitivity using our novel first-order absorption OGTT model (SInew) and GIGt1/2 and Dalla Man’s OGTT model (SI). SInew was highly concordant with SI (R=0.61, P&amp;lt;0.001; Concordance=0.90). When separating subjects by DKA status, there were significant differences in the frequency of remission status (χ2=5.00, P=0.03). Subjects with DKA+REM (98±19 min) had a significantly longer GIGt1/2 compared to those with SH+no-REM (47±9 min, P=0.02). GIGt1/2 between DKA+no-REM (108±46 min) and SH+no-REM was also significantly different (P=0.045). SH+REM showed a statistical trend to be different from SH+no-REM (P=0.07). There were no significant differences identified between DKA+REM, DKA+no-REM and SH+REM. The SInew from our novel OGTT model is highly concordant with SI from Dalla Man’s OGTT model. Our model additionally estimates GIGt1/2 and indicates slower gut glucose absorption is associated with remission. This new model shows that obese African American patients presenting with new-onset DKA or SH may benefit from interventions that target gut glucose absorption. Disclosure D. Stefanovski: None. G.E. Umpierrez: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi US. R.C. Boston: None. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc. Research Support; Self; National Institutes of Health. Funding National Institutes of Health (K12HD085850 to P.V.)

Alterations in plasma non-esterified fatty acid (NEFA) kinetics and relationship with insulin resistance in polycystic ovary syndrome.

Are non-esterified fatty acid (NEFA) kinetics altered in women with polycystic ovary syndrome (PCOS)? Women with PCOS, particularly obese subjects, have dysregulated plasma NEFA kinetics in response to changes in plasma insulin and glucose levels, which are associated with insulin resistance (IR) independently of the fasting plasma NEFA levels. Elevated plasma NEFA levels are associated with IR in many disorders, although the homeostasis of NEFA kinetics and its relationship to IR in women with PCOS is unknown. We prospectively compared insulin sensitivity and NEFA kinetics in 29 PCOS and 29 healthy controls women matched for BMI. This study was conducted in a tertiary institution. Plasma NEFA, glucose and insulin levels were assessed during a modified frequently sampled intravenous glucose tolerance test (mFSIVGTT). Minimal models were used to assess insulin sensitivity (Si) and NEFA kinetics (i.e. model-derived initial plasma NEFA level [NEFA0], phi constant [Φ], reflecting glucose-mediated inhibition of lipolysis and measures of maximum rate of lipolysis [SFFA] and NEFA uptake from plasma [KFFA]). The study provides new evidence that women with PCOS have defective NEFA kinetics characterized by: (i) lower basal plasma NEFA levels, measured directly and modeled (NEFA0), and (ii) a greater glucose-mediated inhibition of lipolysis in the remote or interstitial space (reflected by a lower affinity constant [Φ]). There were no differences, however, in the maximal rates of adipose tissue lipolysis (SFFA) and the rate at which NEFA leaves the plasma pool (KFFA). The differences observed in NEFA kinetics were exacerbated, and almost exclusively observed, in the obese PCOS subjects. Our study did not study NEFA subtypes. It was also cross-sectional and based on women affected by PCOS as defined by the 1990 National Institutes of Health (NIH) criteria (i.e. Phenotypes A and B) and identified in the clinical setting. Consequently, extrapolation of the present data to other phenotypes of PCOS should be made with caution. Furthermore, our data is exploratory and therefore requires validation with a larger sample size. Dysfunction in NEFA kinetics may be a marker of metabolic dysfunction in nondiabetic obese women with PCOS and may be more important than simply assessing circulating NEFA levels at a single point in time for understanding the mechanism(s) underlying the IR of PCOS. This work was supported by NIH grants R01-DK073632 and R01-HD29364 to R.A.; a Career Development Award from MD Medical Group, Moscow, RF, to D.L. and Augusta University funds to Y.-H.C. RA serves as consultant to Ansh Labs, Medtronics, Spruce Biosciences and Latitude Capital. U.E., Z.A., D.L., R.M., Y.-H.C., R.C.B. and Y.D.I.C. have no competing interests to declare. Not applicable.

Febrile neutropenia induces changes in insulin sensitivity similar to obesity

ABSTRACTBackground/aim: To determine insulin sensitivity before chemotherapy and during febrile neutropenia in patients with acute leukemia and to assess its effect on the number of documented infections, the severity of infection and the outcome of the first hospitalization. To compare insulin sensitivity in the study group to a group of patient with obesity.Materials and methods: The study group consisted of 30 (37% of the total number) patients with newly diagnosed acute leukemia. Testing of insulin sensitivity was done before chemotherapy and during febrile neutropenia. Parameters were compared to a group of 30 age, and sex matched patients with obesity.Results: Insulin sensitivity was normal before chemotherapy. Obese patients were characterized by insulin resistance. Febrile neutropenia led to the development of insulin resistance (t = −2.43, p = 0.021). The level of insulin resistance was in positive correlation with fibrinogen (r = 0.59, p < 0.05). Patients with a documented site of infection had higher fasting insulin and an insulin resistance before chemotherapy (t = −2.38, p = 0.024). Insulin sensitivity did not influence outcome of the first hospitalization.Conclusion: Patients with acute leukemia in febrile neutropenia developed changes in insulin sensitivity similar to those seen in obesity. Insulin resistance was present in patients with a documented site of infection, and it worsened with the extent of inflammation. The outcome of the first hospitalization was not affected.

Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: I. Observations Using the Hyperglycemic Clamp

OBJECTIVETo compare insulin sensitivity (M/I) and β-cell responses in youth versus adults with impaired glucose tolerance (IGT) or drug-naïve, recently diagnosed type 2 diabetes.RESEARCH DESIGN AND METHODSIn 66 youth (80.3% with IGT) and 355 adults (70.7% IGT), hyperglycemic clamps were used to measure 1) M/I, 2) acute (0–10 min [first phase]) C-peptide (ACPRg) and insulin (AIRg) responses to glucose, 3) steady-state C-peptide and insulin concentrations at plasma glucose of 11.1 mmol/L, and 4) arginine-stimulated maximum C-peptide (ACPRmax) and insulin (AIRmax) responses at plasma glucose >25 mmol/L. The fasting C-peptide–to–insulin ratio was used as an estimate of insulin clearance.RESULTSInsulin sensitivity was 46% lower in youth compared with adults (P < 0.001), and youth had greater acute and steady-state C-peptide (2.3- and 1.3-fold, respectively; each P < 0.001) and insulin responses to glucose (AIRg 3.0-fold and steady state 2.2-fold; each P < 0.001). Arginine-stimulated C-peptide and insulin responses were also greater in youth (1.6- and 1.7-fold, respectively; each P < 0.001). After adjustment for insulin sensitivity, all β-cell responses remained significantly greater in youth. Insulin clearance was reduced in youth (P < 0.001). Participants with diabetes had greater insulin sensitivity (P = 0.026), with lesser C-peptide and insulin responses than those with IGT (all P < 0.001) but similar insulin clearance (P = 0.109).CONCLUSIONSIn people with IGT or recently diagnosed diabetes, youth have lower insulin sensitivity, hyperresponsive β-cells, and reduced insulin clearance compared with adults. Whether these age-related differences contribute to declining β-cell function and/or impact responses to glucose-lowering interventions remains to be determined.

Endothelial dysfunction of coronary arteries in subjects without diabetes: An association with both insulin resistance and impaired insulin secretion response

AimsThis study was aimed to compare insulin sensitivity and secretion response, lipoprotein and plasminogen activator inhibitor 1 (PAI-1) levels between the subjects with and without coronary artery endothelial dysfunction (ED). MethodsED was detected by intracoronary injection of acetylcholine (ACh) in 47 nondiabetes subjects without stenotic coronary arteries, selected from 316 consecutive patients with coronary angiography performed for suspected coronary artery disease. The subjects were divided into two groups: presence of ACh-induced coronary spasm (group ED+, N = 30) and absence of ACh-induced coronary spasm (group ED−, N = 17). Insulin sensitivity (Si) was evaluated by frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis and by HOMA-IR, insulin secretion by acute insulin response (AIR) (calculated from the first 8 min of FSIGTT) and by disposition index (DI) (Si × AIR). Lipids and PAI-1 levels were determined enzymatically, and LDL particle size by gradient gel electrophoresis. ResultsSi was significantly lower (4.22 ± 0.62 vs 6.98 ± 1.47 min−1/mU/l × 104; p < 0.05) while HOMA-IR was significantly higher in ED + group vs ED− group (2.8 ± 0.3 vs 1.7 ± 0.2; p < 0.05). Simultaneously, AIR and DI was significantly lower in ED + vs ED− groups (p < 0.05 and p < 0.01, respectively). Investigated groups did not differ in fasting lipid levels but ED+ group had significantly smaller LDL particles (p < 0.01) and higher PAI-1 levels (p < 0.05). Regression analysis shown that DI was a strong independent predictor of appearance of ED, together with PAI-1 and LDL particle size. ConclusionsBoth insulin resistance and impairment in insulin secretion response strongly correlate with coronary ED in subjects without diabetes.

Effects of supplemental calcium salts of palm oil and chromium-propionate on insulin sensitivity and productive and reproductive traits of mid- to late-lactating Holstein × Gir dairy cows consuming excessive energy

This experiment compared insulin sensitivity, milk production, and reproductive outcomes in dairy cows consuming excessive energy during mid to late lactation and receiving in a 2 × 2 factorial design (1) concentrate based on ground corn (CRN; n = 20) or including 8% (DM basis) of Ca salts of palm oil (CSPO; n = 20), and (2) supplemented (n = 20) or not (n = 20) with 2.5 g/d of Cr-propionate. During the experiment (d 0-203), 40 multiparous, nonpregnant, lactating 3/4 Holstein × 1/4 Gir cows (initial days in milk = 81 ± 2; mean ± SE) were offered corn silage for ad libitum consumption, and individually received concentrate formulated to allow diets to provide 160% of their daily net energy for lactation requirements. From d -15 to 203, milk production was recorded daily, blood samples collected weekly, and cow body weight (BW) and body condition score (BCS) recorded on d 0 and 203. For dry matter intake evaluation, cows from both treatments were randomly divided in 5 groups of 8 cows each, and allocated to 8 individual feeding stations for 3 d. Intake was evaluated 6 times/group. Glucose tolerance tests (GTT; 0.5 g of glucose/kg of BW) were performed on d -3, 100, and 200. Follicle aspiration for in vitro embryo production was performed via transvaginal ovum pick-up on d -1, 98, and 198. Mean DMI, net energy for lactation intake, as well as BW and BCS change were similar across treatments. On average, cows gained 40 kg of BW and 0.49 BCS during the experiment. Within weekly blood samples, CRN cows had lower serum concentrations of glucose, insulin, fatty acids, and insulin-to-glucose ratio compared with CSPO cows, suggesting increased insulin sensitivity in CRN cows. During the GTT, insulin-sensitivity traits were also greater in CRN versus CSPO cows. Supplemental Cr-propionate resulted in lower serum insulin concentrations and insulin-to-glucose ratio within CRN cows only, indicating that Cr-propionate improved basal insulin sensitivity in CRN but not in CSPO cows. During the GTT, however, Cr-propionate supplementation reduced hyperinsulinemia and insulin-to-glucose ratio across CSPO and CRN cows. Milk production, as well as number of viable oocytes collected and embryos produced within each aspiration, were not affected by treatments. Hence, replacing corn by Ca salts of palm oil in the concentrate did not improve insulin sensitivity in Holstein × Gir dairy cows consuming excessive energy during mid to late lactation, whereas Cr-supplementation was effective in improving basal insulin sensitivity in cows not receiving Ca salts of palm oil.

Effects of concentrate type and chromium propionate on insulin sensitivity, productive and reproductive parameters of lactating dairy cows consuming excessive energy

This experiment compared insulin sensitivity parameters, milk production and reproductive outcomes in lactating dairy cows consuming excessive energy, and receiving in a 2×2 factorial arrangement design: (1) concentrate based on ground corn (CRN; n=13) or citrus pulp (PLP; n=13), and (2) supplemented (n=14) or not (n=12) with 2.5 g/day of chromium (Cr)-propionate. During the experiment (day 0 to 182), 26 multiparous, non-pregnant, lactating Gir×Holstein cows (initial days in milk=80±2) were offered corn silage for ad libitum consumption, and individually received concentrate formulated to allow diets to provide 160% of their daily requirements of net energy for lactation. Cow BW and body condition score (BCS) were recorded weekly. Milk production was recorded daily and milk samples collected weekly. Blood samples were collected weekly before the morning concentrate feeding. Glucose tolerance tests (GTT; 0.5 g of glucose/kg of BW) were performed on days −3, 60, 120 and 180. Follicle aspiration for in vitro embryo production was performed via transvaginal ovum pick-up on days −1, 82 and 162. No treatment differences were detected (P⩾0.25) for BW and BCS change during the experiment. Within weekly blood samples, concentrations of serum insulin and glucose, as well as insulin : glucose ratio were similar among treatments (P⩾0.19), whereas CRN had less (P<0.01) non-esterified fatty acid concentrations compared with PLP (0.177 v. 0.215 mmol/l; SEM=0.009). During the GTT, no treatment differences were detected (P⩾0.16) for serum glucose concentration, glucose clearance rate, glucose half-life and insulin : glucose ratio. Serum insulin concentrations were less (P=0.04) in CRN supplemented with Cr-propionate compared with non-supplemented CRN (8.2 v. 13.5 µIU/ml, respectively; SEM=1.7), whereas Cr-propionate supplementation did not impact (P=0.70) serum insulin within PLP cows. Milk production, milk fat and solid concentrations were similar (P⩾0.48) between treatments. However, CRN had greater (P<0.01) milk protein concentration compared with PLP (3.54% v. 3.14%, respectively; SEM=0.08). No treatment differences were detected (P⩾0.35) on number of viable oocytes collected and embryos produced within each aspiration. In summary, feeding a citrus pulp-based concentrate to lactating dairy cows consuming excessive energy did not improve insulin sensitivity, milk production and reproductive outcomes, whereas Cr-propionate supplementation only enhanced insulin sensitivity in cows receiving a corn-based concentrate during a GTT.

Effect of Iron Chelation Therapy on Glucose Metabolism in Non-Transfusion-Dependent Thalassaemia

Aims: To compare insulin sensitivity, β-cell function and iron status biomarkers in non-transfusion-dependent thalassaemia (NTDT) with iron excess during pre- and post-iron chelation. Methods: Subjects with NTDT, aged older than 10 years, with serum ferritin >300 ng/ml, were included. Iron chelation with deferasirox (10 mg/kg/day) was prescribed daily for 6 months. Results: Ten patients with a median age of 17.4 years were enrolled. The comparison between pre- and post-chelation demonstrated significantly lower iron load: median serum ferritin (551.4 vs. 486.2 ng/ml, p = 0.047), median TIBC (211.5 vs. 233.5 µg/dl, p = 0.009) and median non-transferrin binding iron (5.5 vs. 1.4 µ<smlcap>M</smlcap>, p = 0.005). All patients had a normal oral glucose tolerance test (OGTT) both pre- and post-chelation. However, fasting plasma glucose was significantly reduced after iron chelation (85.0 vs.79.5 mg/dl, p = 0.047). MRI revealed no significant changes of iron accumulation in the heart and liver after chelation, but there was a significantly lower iron load in the pancreas, assessed by higher T2* at post-chelation compared with pre-chelation (41.9 vs. 36.7 ms, p = 0.047). No adverse events were detected. Conclusions: A trend towards improving insulin sensitivity and β-cell function as well as a reduced pancreatic iron load was observed following 6 months of iron chelation (TCTR20160523003).

Evaluation of an Insulin Sensitivity Index from the Short Intravenous Glucose Tolerance Test

The aim of this analysis was to compare insulin sensitivity indices calculated from a short (50 min), insulin‐modified intravenous glucose tolerance test (IVGTT; Tura SI) to that from a full 180 min IVGTT using minimal model analysis (MM SI), as well as the Matsuda Index (M‐SI) from a 120 min liquid meal tolerance test (Maki et al. Diabetes Tech Ther 2011;13:661–6). The IVGTT included glucose (0.3 g/kg, t = 0 min) and regular human insulin (0.03 U/kg; t = 20 min) injection with samples collected at frequent intervals over 180 min. Tura SI was calculated as the fractional glucose disappearance rate/average increment in plasma insulin, both from 10–50 min. The MINMOD MILLENNIUM program (v6.02) was used to calculate MM SI. Subjects were overweight or obese men (n = 8) and women (n = 16) without diabetes who agreed to participate in a substudy after completing a dietary intervention trial. Mean ± SEM MM SI was 3.94 ± 3.38 × 10−4 L*min−1*mU−1, age was 48.9 ± 2.0 y and body mass index was 30.8 ± 0.6 kg/m2. Pearson correlation coefficients were: Tura SI with MM SI r = 0.963, Tura SI with M‐SI r = 0.803, and MM SI with M‐SI r = 0.776, all p &lt; 0.001. Thus, Tura SI from the first 50 min of an insulin‐modified IVGTT correlates very strongly with 180 min MM SI (reference method), and the relationship between Tura SI with M‐SI was similar in magnitude to that between MM SI and M‐SI. These results suggest that the short IVGTT may be used as a less costly and time‐consuming alternative to the 180 min IVGTT for assessment of whole‐body insulin sensitivity.Support or Funding InformationIngredion, Westchester, IL

Anthropometric measurements for assessing insulin sensitivity on patients with metabolic syndrome, sedentaries and marathoners.

The diagnosis of low insulin sensitivity is commonly done through the HOMA-IR index, in which fasting insulin and glucose blood levels are evaluated. Insulin and blood glucose levels are used for insulin sensitivity assessment by surrogate methods (HOMA-IR, Matsuda, etc), but anthropometric measurements like body weight, height and waist circumference are not considered, even if these variables also are related to low insulin sensitivity and metabolic syndrome. In this study we evaluate the impact of anthropometric measurements on the HOMA-IR, Matsuda and Caumo indexes to estimate insulin sensitivity. Specifically, we compare insulin sensitivity indexes with and without the anthropometric measurements in their equations on three different groups: patients with metabolic syndrome, sedentaries and marathoners. Results show relationships between anthropometric variables and insulin sensitivity indexes. On the other hand, subjects are mapped differently for insulin sensitivity assessment when anthropometric variables are taken into account. In addition, subjects diagnosed with normal insulin sensitivity could be considered as having low insulin sensitivity when anthropometric variables are considered.

Birth Weight, Insulin Resistance, and Blood Pressure in Late Preterm Infants.

This study aims to compare insulin sensitivity, lipid profile, and blood pressure in late preterm infants born at appropriate for gestational age (AGA) and small for gestational age (SGA). We conducted a prospective, observational study on AGA and SGA late preterm infants. Blood pressure, fasting blood glucose, insulin, insulin-like growth factor 1 (IGF-1), insulin resistance, and lipid profile were measured on the 1st day and in the 2nd week of life. Overall 81 infants (41 AGA and 40 SGA) were included in the study. At the time of enrollment, there was no difference in blood pressure, insulin resistance, and lipid profile. At follow-up SGA patients had significantly decreased diastolic blood pressure (48 ± 11 mm Hg vs. 42 ± 11 mm Hg, p = 0.04), and decreased IGF-1 (139 ng/mL [119-153] vs. 124 ng/mL [115-138], p = 0.05). No linear association was found between the insulin resistance and either birth weight percentile, day of life, or average 1st week daily caloric intake. As compared with AGA, SGA late preterm infants had lower diastolic blood pressure and lower IGF-1 during the 2nd week of life, but similar insulin resistance and lipid profile. We speculate that although metabolic derangements in SGA infants could have occurred at a much earlier age in fetal life, their manifestations may not be present in the immediate postnatal life.

Insulin Resistance Alters Islet Morphology in Nondiabetic Humans

Type 2 diabetes is characterized by poor glucose uptake in metabolic tissues and manifests when insulin secretion fails to cope with worsening insulin resistance. In addition to its effects on skeletal muscle, liver, and adipose tissue metabolism, it is evident that insulin resistance also affects pancreatic β-cells. To directly examine the alterations that occur in islet morphology as part of an adaptive mechanism to insulin resistance, we evaluated pancreas samples obtained during pancreatoduodenectomy from nondiabetic subjects who were insulin-resistant or insulin-sensitive. We also compared insulin sensitivity, insulin secretion, and incretin levels between the two groups. We report an increased islet size and an elevated number of β- and α-cells that resulted in an altered β-cell–to–α-cell area in the insulin- resistant group. Our data in this series of studies suggest that neogenesis from duct cells and transdifferentiation of α-cells are potential contributors to the β-cell compensatory response to insulin resistance in the absence of overt diabetes.

Decreased insulin sensitivity in young adults born through in vitro fertilisation (IVF) and higher systolic blood pressure following high fat overfeeding

Risk factors for type 2 diabetes (T2DM) and cardiovascular disease (CVD) may be increased in those conceived by IVF. The study aims to compare insulin sensitivity and metabolic risk factors in young adults conceived either naturally (controls) or by IVF compared while consuming a standard energy balanced diet and following 3-days of high fat overfeeding.

1321 PREDICTORS OF DIRECTLY MEASURED INSULIN RESISTANCE IN AT-RISK LATINOS WITH AND WITHOUT HEPATITIS C (HCV) INFECTION

Background and Aims: HCV is associated with insulin resistance and disproportionately affects Latinos, who in turn have higher rates of diabetes. Factors predictive of insulin resistance in HCVinfected Latinos are not well understood. We aim to compare insulin sensitivity using direct measurements, and assess host and viral factors associated with insulin resistance in Latinos. Methods: 123 non-cirrhotic, non-diabetic Latinos (52 with HCV) were enrolled. All subjects underwent clinical and metabolic evaluation including oral glucose tolerance test and insulin sensitivity by steady-state plasma glucose (SSPG) concentration during the insulin suppression test. Patients in the lowest tertile of SSPG were defined as insulin sensitive (IS) and in the highest tertile as insulin resistant (IR). Results: Overall patient characteristics were: mean age 43±10 years, 64% male, and BMI 27±5 Kg/m. Among HCV-positive patients, 67% were genotype 1, mean log10 HCV viral load was 5.83 IU/mL, and mean ALT 89±73 IU/mL. The mean SSPG in IS (N=40) was of 65±14mg/dL and in IR (N=41) was 239±35mg/dL. On univariable analysis, IS and IR patients were similar with respect to age, family history of diabetes, and tobacco use. However, IR was positively associated with HCV status (OR 1.83, 95%CI 0.7–4.2), female gender (OR 2.38, 95%CI 0.9–5.8), waist circumference (OR 1.21, 95%CI 1.1–1.3), serum LDL (OR 1.02, 95%CI 1.00–1.03), and triglycerides (OR 1.02, 95%CI 1.01–1.04); and negatively associated with HDL (OR 0.93, 95%CI 0.89–0.97), and current alcohol use (OR 0.43, 95%CI 0.97–1.04). On multivariable analysis, controlling for age and family history of diabetes, female gender (OR 13.74, 95%CI 1.99–94.9, p = 0.008), HCV infection (OR 9.13, 95%CI 1.2– 70.1, p = 0.03), waist circumference (OR 1.14, 95%CI 1.04–1.24, p = 0.006), and triglycerides (OR 1.02, 95%CI 1.00–1.04, p = 0.04) were significantly associated with IR. Conclusions: Along with host factors, HCV infection was associated with nine-fold higher odds of directly measured insulin resistance in Latinos. Although male gender is associated with higher diabetic rates, female gender was a strong predictor of insulin resistance among Latinos. The role of other gender-specific factors influencing insulin resistance in this population requires further investigation. Grant support: National Institute of Health, R01-DK074673 (M.K.) and American Diabetes Foundation 1–08-CR-30 (M.K.).

Increased prevalence of impaired fasting glucose in MEN1 gene mutation carriers

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome characterized by parathyroid, gastroenteropancreatic, pituitary and adrenal tumours. Cardiovascular disease has been identified as an important cause of death in MEN1 patients. Menin, the product of the MEN1 gene, is a co-activator for peroxisome proliferator-activated receptor-γ and the vitamin D receptor, which are involved in glucose metabolism. We aimed to compare insulin sensitivity and prevalence of impaired fasting glucose and diabetes mellitus between MEN1 patients and controls. Cross-sectional study. Sixty-three MEN1 gene mutation carriers (44% men, mean age 41 years) from 22 kindreds and 126 unrelated controls matched for gender, age and BMI. Fasting glucose levels were categorized and compared using WHO criteria. Homeostasis model assessment (HOMA) was used as a measure of insulin resistance. Homeostasis model assessment was significantly increased in MEN1 patients compared with controls (3·0 ± 2·0 vs 2·0 ± 1·0, P < 0·05). In MEN1 patients, HOMA was associated with BMI, but not with age, calcium and gastrin levels. Using logistic regression analysis, the presence of hyperparathyroidism, pancreatic lesions and various other manifestations was not associated with HOMA. Impaired fasting glucose was more prevalent in MEN1 compared with controls (17%vs 6%, P < 0·05). Three MEN1 patients (5%) compared with four controls (3%) were diabetic (not significant). Multiple endocrine neoplasia type 1 patients had decreased insulin sensitivity and higher prevalence of impaired fasting glucose compared with controls, which was unrelated to MEN1 manifestations. Impaired glucose metabolism may result in increased risk of cardiovascular disease in MEN1 patients.

Vitamin D, Insulin Secretion, Sensitivity, and Lipids

OBJECTIVEVitamin D deficiency is associated with an unfavorable metabolic profile in observational studies. The intention was to compare insulin sensitivity (the primary end point) and secretion and lipids in subjects with low and high serum 25(OH)D (25-hydroxyvitamin D) levels and to assess the effect of vitamin D supplementation on the same outcomes among the participants with low serum 25(OH)D levels.RESEARCH DESIGN AND METHODSParticipants were recruited from a population-based study (the Tromsø Study) based on their serum 25(OH)D measurements. A 3-h hyperglycemic clamp was performed, and the participants with low serum 25(OH)D levels were thereafter randomized to receive capsules of 20,000 IU vitamin D3 or identical-looking placebo twice weekly for 6 months. A final hyperglycemic clamp was then performed.RESULTSThe 52 participants with high serum 25(OH)D levels (85.6 ± 13.5 nmol/L [mean ± SD]) had significantly higher insulin sensitivity index (ISI) and lower HbA1c and triglycerides (TGs) than the 108 participants with low serum 25(OH)D (40.3 ± 12.8 nmol/L), but the differences in ISI and TGs were not significant after adjustments. After supplementation, serum 25(OH)D was 142.7 ± 25.7 and 42.9 ± 17.3 nmol/L in 49 of 51 completing participants randomized to vitamin D and 45 of 53 randomized to placebo, respectively. At the end of the study, there were no statistically significant differences in the outcome variables between the two groups.CONCLUSIONSVitamin D supplementation to apparently healthy subjects with insufficient serum 25(OH)D levels does not improve insulin sensitivity or secretion or serum lipid profile.