Predictors of Insulin Resistance and Metabolic Complications in Polycystic Ovarian Syndrome in an Eastern Indian Population

The purpose of this study was to assess the predictive values of central obesity and hyperandrogenemia in development of insulin resistance and dyslipidemia in the polycystic ovarian syndrome (PCOS) patients in our region. Differences of fasting blood glucose level, insulin resistance index HOMA-IR, lipid parameters, waist hip ratio (WHR), body mass index, LH/FSH ratio and testosterone levels between 45 PCOS cases and 35 age matched controls were obtained. Strength of association between different parameters in the case group was assayed by Pearson’s correlation analysis. Dependence of insulin resistance and WHR on different predictors was assessed by multiple linear regression assay. Total cholesterol, LDL cholesterol, LH, FSH, LH/FSH ratio, WHR and insulin resistance were significantly higher in the case group (p < 0.05). Serum testosterone showed strong correlation with insulin resistance and LH/FSH ratio (r = 0.432 and 0.747, p = 0.01 and 0.001 respectively) in the PCOS patients while WHR and serum testosterone level stood out to be most significant predictors for the insulin resistance (β = 0.361 and 0.498; p = 0.048 and 0.049 respectively). Hyperandrogenemia and central obesity were the major factors predicting development of insulin resistance and its related metabolic and cardiovascular complications in our PCOS patients. We suggest early monitoring for androgen level and WHR in these patients for predicting an ensuing insulin resistance and modulating the treatment procedure accordingly to minimise future cardiovascular risks.     

Tumor Necrosis Factor-Α, Interleukin-6, C-Reactive Protein Levels and Insulin Resistance Associated with Type 2 Diabetes in Abdominal Obesity Women

We aim to investigate the association between elevated tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and high sensitivity-C-reactive protein (hs-CRP) with type 2 diabetes mellitus (T2DM) in abdominal obesity (AO) women subjects. A total of 428 AO subjects (age 48.4 ± 10.2 years), and 107 non-AO women subjects (age 48.8 ± 11.8 years) were enrolled for the all biochemistry testing, inflammatory cytokines, fasting insulin and Homeostasis Model Assessment of insulin resistance (HOMA-IR). Body mass index, waist circumference (WC), blood pressure (BP), plasma glucose (Glu), triglyceride (TG), insulin, HOMA-IR and inflammatory cytokines were significantly higher and lower total antioxidant capacity, HDL-C in AO subjects (p < 0.05). WC was significantly correlated with BP, Glu, TG, LDL-C, insulin, HOMA-IR, TNF-α, IL-6 and negative correlation with HDL-C in AO subjects. Elevation of TNF-α, IL-6, hs-CRP and insulin resistance were significantly associated with T2DM in AO subjects, after adjusting with insulin resistance, increased oxidative stress, elevated TG and reduced HDL-C by using multiple logistic regression analysis. In conclusions, elevation of inflammatory cytokines, oxidative stress and insulin resistance were associated with T2DM in AO women subjects. These inflammatory cytokines are positively associated with T2DM and may have a causal relation with an increased oxidative stress and insulin resistance in these AO women subjects.     

Circadian Rhythm of Serum Cortisol in Female Patients with Fibromyalgia Syndrome

Fibromyalgia syndrome (FMS) patients have disturbed sleep patterns which may lead to altered circadian rhythm in serum cortisol secretion. The aim of this study was to assess circadian changes, if any, in serum cortisol levels in female patients with FMS. Cortisol levels were estimated every 6 h during 24 h period; in 40 female patients satisfying ACR criteria for FMS (Age 36.4 ± 9.9), and 40 healthy females without FMS (Age 33.8 ± 11.1). A significant difference in the night time serum cortisol level was observed among the patients and control groups (patients, 12.9 ± 9.7 controls 5.8 ± 3.0; p < 0.01). However, no significant difference was found in serum cortisol levels in patients and control groups in the morning (patients, 28.4 ± 13.2 controls, 27.6 ± 14.5; p > 0.05), afternoon (patients, 14.4 ± 5.6 controls, 14.0 ± 6.6; p > 0.05) and evening hours (patients, 10.9 ± 5.8 controls, 8.9 ± 3.6; p > 0.05). It could be concluded that there is an abnormality in circadian secretion of cortisol in female FMS patients.     

Circadian Periodicity of Circulating Plasma Lipid Peroxides,Uric Acid and Ascorbic Acid in Renal Stone Formers

Circadian periodicity of plasma lipid peroxides and serum ascorbic acid and uric acid levels were studied in one hundred renal stone formers (55 women and 45 men; age 20–60 years) and 50 clinically healthy volunteers (21 women and 29 men; age 21–45 years) with diurnal activity from 06:00 to 22:00 and nocturnal rest. A marked circadian variation was demonstrated by population-mean-cosinor for all studied variables in stone formers and healthy subjects. By comparison to the healthy controls, parameter tests indicate that the stone formers had a higher MESOR (±SE) of MDA (2.90 ± 0.03 vs. 2.28 ± 0.06; F = 94.929, p < 0.001), a lower MESOR of serum ascorbic acid (0.722 ± 0.010 vs. 0.839 ± 0.10; F = 32.083, p < 0.001), and a similar MESOR of serum uric acid. Furthermore, the patients also differed from the healthy subjects in terms of their circadian amplitude and acrophase (tested jointly) of all three variables (p < 0.001). The demonstration herein of a circadian rhythm in MDA, serum ascorbic and uric acid suggests that these variables could also serve as markers to optimize the timing of treatment and to assess the patient’s response to treatment for further management.     

Implications of ACE (I/D) Gene Variants to the Genetic Susceptibility of Coronary Artery Disease in Asian Indians

Angiotensin-1-converting enzyme (ACE) gene has established substantial attention in the recent years as a candidate gene for hypertension, cardiovascular diseases and type 2 diabetes. The aim of the present study was to investigate the association of ACE (I/D) polymorphism with coronary artery disease (CAD) in a north Indian population. A total of 662 subjects (330 CAD patients and 332 healthy controls) were examined for association of ACE gene (I/D) polymorphism and environmental risk factors. The mean age of the CAD patients and control subjects was 60.53 ± 8.6 years and 56.55 ± 7.7 years, respectively (p = 0.000). Anthropometric and demographic data showed BMI values significantly higher among CAD patients and control subjects (26.98 ± 4.9 vs 24.04 ± 4.7, p = 0.000). We observed pronounced central obesity in both CAD patients and controls, even at the lowest BMI values (<23 kg/m²). Dyslipidemia was highly prevalent in CAD patients compared to control subjects. Genotypic data showed significantly higher frequency of DD genotype in CAD patients than that of control subjects (40 vs 28.3 %). No significant difference was observed in the distribution of ID genotypes between CAD patients and control subjects. Logistic regression analysis of data demonstrate that DD genotype was associated with 1.8 fold increased risk of development of CAD in Asian Indians (OR 1.8; 95 % CI 1.22–2.66; p = 0.003). The frequency of D allele was significantly higher in CAD patients (p = 0.001). No significant difference was observed in the clinical and biochemical characteristics of CAD patients and controls when the data was stratified according to the genotypes of ACE gene. In conclusion, DD genotype of ACE gene may be associated with increased risk of CAD in Asian Indian population.     

Diagnostic Value of Lactate Levels in Acute Abdomen Disorders

The supply of oxygen is limited in certain intra abdominal conditions due to direct vascular invasion or inflammatory process, resulting in high lactate levels. Aim of this study was to find the predictive value of lactate levels in the peritoneal fluid (PF) and blood of patients with acute abdomen. The study comprised of fifty patients with acute abdominal conditions, admitted in emergency ward of tertiary care hospital, thirty patients were with surgical abdomen (group I) and twenty patients with non surgical abdomen (group II). Lactate was estimated in PF and blood on Blood Gas Analyzer (NOVA, M-7). The mean lactate levels in PF were significantly higher in group I as compared to group II (14.65 ± 1.195 vs. 5.92 ± 0.97 mmol/L, p < 0.001). There was no significant difference in blood lactate levels in both the groups. When PF and blood lactate levels were compared within groups, we found that PF levels were significantly higher than blood in group I (14.65 ± 1.195 vs. 3.85 ± 0.54 mmol/L, p < 0.001) but not in group II (5.92 ± 0.97 vs. 4.36 ± 0.95 mmol/L). Diagnostic value was obtained using ROC curve. Cut off values obtained for PF lactate, difference and ratio of PF and blood lactate (≥6.4 mmol/L, ≥3.3 and ≥2.1 respectively) are at very high degree of sensitivity and specificity. So it can be useful marker of surgical emergency in patients with acute intra abdominal pathology, especially in clinically ill patients or in whom physical examination is not yielding because of neurologic disorders or unresponsiveness.     

Biochemical Profile of Nonalcoholic Fatty Liver Disease Patients in Eastern India with Histopathological Correlation

Aminotransferase assay is often used as a screening test as well as an endpoint for resolution of disease in nonalcoholic fatty liver disease (NAFLD). Aim of the study was to evaluate the relationship of transaminase level with metabolic variables and histology in NAFLD. Single center observational study was conducted in a gastroenterology clinic at Cuttack in coastal Odisha. Subjects were consecutive patients presenting with functional bowel disease and undergoing abdominal sonography. All participants were evaluated for the presence of metabolic syndrome (MS), insulin resistance, liver function test and lipid profile. Various parameters were compared between NAFLD subjects and controls. 53.5 % of NAFLD had normal serum transaminases, whereas 20.8 % of healthy controls had transaminitis. NAFLD patients had significantly higher BMI, fasting plasma glucose, serum transaminases, serum triglycerides, serum insulin and homeostatic model assessment (HOMA) IR than controls. NAFLD patients who had transaminitis had significantly higher incidence of MS and higher mean HOMA IR than those without. There was no significant difference in histopathological features between NAFLD with and without transaminitis. To conclude, over half of NAFLD subjects do not have transaminitis while transaminitis is present in a fifth of healthy people without fatty liver. Hence serum transaminase should not be used as screening test for NAFLD. NAFLD patients with transaminitis had a higher incidence of MS and insulin resistance than those without. However, there was no significant difference in histopathological features between these two groups.     

A Study to Evaluate Lipid Profile in Treatment Naïve HIV Positive Patients

HIV infection is associated with lipid abnormalities in treatment naïve patients. CD4 count is used for monitoring the HIV infection. Primary objective was to evaluate and correlate lipid profile and CD4 counts in HIV infection. Secondary objective was to evaluate the feasibility of using Lipid profile to monitor the HIV infected treatment naïve patients instead of CD4 counts. 112 patients were selected based on a criteria from ART center in tertiary care center. CD4 counts were assessed and Lipid profile was evaluated enzymatically. A correlation study was done between the lipid profile and the CD4 count and clinical stages of infection. Cholesterol showed no significant correlation in any stage. HDL-C showed significant correlation (p < 0.05) with stage 2 and 4 disease. LDL-C showed no significant correlation in any stage. TGL showed significant correlation (p < 0.05) at stage 4 disease. Hence, HDL-C and TGL can be used as indicators of lipid status and for infection progression in treatment naive HIV patients, while Cholesterol and LDL-C has no role to play.     

Hypoadiponectinemia in Obesity: Association with Insulin Resistance

Obesity is risk factor for insulin resistance, diabetes, and other chronic diseases. Adiponectin, an adipose-specific protein with antiatherogenic and antiinflammatory effects, were found to be associated with obesity, type 2 diabetes, and insulin resistance. Our aim to identify possible relationships between circulating adiponectin and obesity as well as obesity related phenotypes. A total of 642, obese and non-obese individuals were included in this cross-sectional study. Hormone and glucose levels were estimated using standard protocols. The adiponectin levels showed a significant decrease with increasing quartiles of insulin resistance index. Subjects in lowest quartile of adiponectin level had a significantly higher risk than those in the highest quartile, with higher body mass index, waist circumference, blood pressure, percentage body fat, fat mass, fasting insulin, insulin resistance index, total cholesterol (p < 0.001), low density lipoprotein–cholesterol (p = 0.001), very low density lipoprotein–cholesterol (p = 0.002), and Triglyceride (p = 0.002). The present study indicates that adiponectin is significantly associated with obesity, insulin resistance and other obesity related phenotypes.     

The Association Between Small Dense Low Density Lipoprotein and Coronary Artery Disease in North Indian Patients

Pathogenesis of coronary artery disease (CAD) is multi-factorial and several conventional risk factors have been ascribed; LDL-C being one of the important risk factor. However Indian population studies with established CAD often show LDL levels within normal range in patients with proven CAD. We hypothesized that Small dense low density lipoprotein (sdLDL) being more atherogenic might correlate more strongly to the occurrence and severity of CAD. The aim of the study was to evaluate the association between serum small dense LDL level and angiographically documented coronary artery disease. This is a cross sectional case control study in which sdLDL were measured in 126 patients with CAD and in 64 patients without CAD. Total cholesterol, HDL Cholesterol, LDL cholesterol and triglycerides were measured by standard methods along with other traditional risk factors. Direct quantitative measurement of sdLDL was done by enzymatic analysis. Mean sdLDL level was higher in patients with coronary stenosis than patients without coronary stenosis (16.3 ± 6.8 vs. 10.1 ± 5.7 mg/dL respectively, (p < 0.001). There was significant correlation between mean sdLDL and severity of CAD as assessed by syntax score with mean sdLDL level in low, intermediate and high syntax score being 15.0 ± 5.8, 20.1 ± 6.7 and 22.7 ± 7.3 mg/dL respectively (p value <0.001). A cut off value of 10.02 mg/dL was associated with presence of CAD (95 % CI 0.82–0.93, p < 0.001) using ROC curve. In conclusion Indian patients with established CAD have higher sdLDL levels compared to individuals without CAD despite having comparable LDL levels.     

Homeostatic Model Assessment-Insulin Resistance (HOMA-IR 2) in Mild Subclinical Hypothyroid Subjects

Despite various studies with conflicting results, the effect of thyroid hormones on lipids and insulin levels in dysthyroidism is of great interest. This case control study was aimed to perceive the existence of IR and dyslipidemia in mild subclinical hypothyroid subjects (TSH ≤ 9.9 µIU/ml) as compared to their age and gender matched euthyroid controls. Basic demographic information like height, weight was recorded. Serum samples of all the subjects were assayed for thyroid profile, lipid profile, blood glucose, HbA1C and insulin. BMI and insulin resistance was calculated. Compared to controls patients with mild subclinical hypothyroidism demonstrated hyperinsulinemia and dyslipidemia observed by the higher LDL cholesterol. A significantly positive correlation was observed for HOMA-IR with TSH and LDL cholesterol. Hence, even in the mild subclinical hypothyroid state assessment of thyroid function should be combined with estimation of plasma glucose, insulin and serum lipids to monitor and prevent its associated effects.     

Association of Iron Overload with Oxidative Stress,Hepatic Damage and Dyslipidemia in Transfusion-Dependent β-Thalassemia/HbE Patients

Blood transfusion can be a life-saving therapy for β-thalassemia major and β-thalassemia/HbE (β-TM) patients with chronic anemia, major caused severe iron overload particularly in β-TM patients received only blood transfusion therapy. We aim to evaluate the association of iron overload with oxidative stress, liver damage, and elevated very low density lipoprotein cholesterol (VLDL-C) in transfusion-dependent β-TM patients. Serum ferritin, malondialdehyde (MDA), liver profiles, triglycerides levels, and VLDL-C were significantly higher while total cholesterol, low-density lipoprotein cholesterol, high density lipoprotein cholesterol and total antioxidant capacity were lower in β-TM than controls. Serum ferritin was significantly correlated with MDA, liver enzymes and lipid profiles (p < 0.05). Multiple forward stepwise linear regression analyses of the significant variables showed that in these β-TM patients, independent predictors of iron overload were MDA (β = 0.410, r ² = 0.671, p < 0.001), ALT (β = 0.493, r ² = 0.578, p < 0.001), and VLDL-C (β = 0.253, r ² = 0.711, p < 0.001). In conclusion, iron overload associated with increased oxidative stress, lipid peroxidation, liver damage, decreased TC, LDL-C, HDL-C and over production of VLDL-C, is significantly problem in transfusion-dependent β-TM patients. These appeared the major cause of future morbidity and mortality in β-TM patients.     

Preliminary studies on serum lipids, apolipoprotein-B and oxidative stress in xanthelasma

Serum lipid profile, apolipoprotein-B (apo-B), malondialdehyde levels(MDA) and superoxide dismutase (SOD) activity were assessed in 12 cases of xanthelasma with and without coronary artery disease (CAD)/hypertension (HTN) and results are compared with healthy controls. Dyslipidemia was found in 65% cases of xanthelasma as compared to 20% healthy controls. Xanthelasma patients had significantly high malondialdehyde (MDA) levels (p<0.01) and significantly decreased (p<0.05) SOD activity as compared to controls. Among xanthelasma patients, xanthelasma with CAD/HTN showed higher total cholesterol (236±32.7 vs 188±24.7 mg/dl), low density lipoprotein cholesterol (157±35.5 vs 113±16 mg/dl) and Apo-B (120.5±9.4 vs 114±19.2 mg/dl) levels as compared to xanthelasma without CAD/HTN. Results of our study indicate that xanthelasma patients with increased apo-B, MDA and decreased SOD need cardiovascular monitoring.     

The Effects of Onion Consumption on Prevention of Nonalcoholic Fatty Liver Disease

It is well known that dietary intakes play a pivotal role in pathogenesis of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH); however, the role of each component of diet has not yet been elucidated. Our objective was to evaluate the effects of onion consumption on prevention of NAFLD/NASH development. Sprague–Dawley rats were fed either high-fat, high sugar diet (model group), or high-fat, high sugar diet plus 7% onion powder (model + onion), or chow diet ad libitum for 7 weeks. Serum levels of fasting glucose, triglyceride, cholesterol, liver enzymes, insulin, and hepatic tumor necrosis factor-alpha (TNF-α) gene expression were determined. Hepatic histology was examined by H&E stain. Model + onion group had significantly lower hepatic steatosis, ballooning, lobular inflammation, and portal inflammation (p < 0.001), lower hepatic TNF-α gene expression (p < 0.001), lower plasma levels of ALT (p = 0.026), AST (p = 0.041), insulin (p < 0.001), TG (p = 0.041), and glucose (p = 0.009) compared with model group; however, weight gain, food intake, plasma total cholesterol and LDL levels were not significantly different between these two groups. Our data indicate that regular consumption of onion can prevent NAFLD even in the presence of the other risk factors such as obesity, hypercholesterolemia, and high energy, fat, and sugar intakes.     

Clinico-Biochemical Correlation Between Psoriasis and Insulin Resistance

Psoriasis is a chronic inflammatory disease associated with an increased insulin resistance, obesity and cardiovascular risk. The present study was aimed to assess insulin resistance and pattern of body fat deposition in psoriasis. Body mass index (BMI) and waist circumference (WC) were measured in 40 psoriatic patients and 46 age- and sex-matched control subjects. Fasting blood glucose (FBG) and serum insulin level were measured by standard photometric method and ELISA respectively. HOMA-IR (homeostatic model of insulin resistance) was calculated by appropriate software. The results indicated that case and control groups were comparable in terms of age and sex (p = 0.934) with an increased prevalence of psoriasis among male subjects (60 %). FBG and mean WC between the two groups were statistically not significant (p value = 0.271 and 0.21 respectively). BMI was significantly higher in case group compared to the control group (p = 0.049). Serum insulin level and insulin resistance in the psoriatic patients were significantly higher (p value <0.001). Multiple regression analysis revealed that insulin resistance (measured by HOMA) was dependent on BMI and WC at a significance level of p < 0.001 and 0.043 respectively. Therefore, the psoriatic patients in this region have significantly high amount of fasting serum insulin level along with an increased IR though their FBG level remains normal. Furthermore, these abnormalities are significantly dependent on total body fat as well as abdominal fat deposits. We suggest that psoriatic patients need to be evaluated for metabolic syndrome and managed accordingly.     

Correlation of Serum Homocysteine Levels with the Severity of Coronary Artery Disease

Coronary artery disease (CAD) has become the most common cause of mortality in the entire world. Homocysteine is implicated as an early atherosclerotic promoter. We studied the relationship between levels of serum homocysteine with severity of coronary artery disease. Total of 70 subjects who scheduled for coronary angiogram consented to participate in this study. In all the patients Gensini scoring system was used to assess the severity of CAD. Venous samples were taken from the patients in fasting state before angiography. Homocysteine levels in patients were measured by enzyme linked immunosorbant method and were compared with respective Genseni scores of participants. Fasting serum homocysteine levels in CAD patients were significantly higher than patients without coronary artery disease (p < 0.001). Also Homocyseine levels correlated significantly with increasing severity of CAD (p < 0.001). Serum homocysteine levels correlated well with the severity of CAD.     

Assessment of Hematological Parameters in Pulmonary Tuberculosis Patients

The aim of the study was the assessment of hematological parameters in pulmonary tuberculosis patients. Forty patients diagnosed with tuberculosis were recruited from the Institute of Thoracic Medicine on the basis of history, clinical examination, chest radiography, sputum examination and related laboratory parameters and were compared with age and sex matched healthy volunteers (n = 40). Hematological parameters and CRP in tuberculosis patients were determined. The mean values for serum hemoglobin level, RBC count and platelet count in PTB was found to be less (p < 0.001). Erythrocyte sedimentation rate (ESR), plasma C-reactive protein, WBC count in PTB subjects was increased (p < 0.001 for ESR & CRP, p < 0.05 for WBCs) and all were statistically significant. This study demonstrated that serum hemoglobin level, RBC count and platelet count was decreased in tuberculosis patients whereas ESR, CRP and WBC count was increased when compared with healthy controls.     

Prevalence of insulin resistance in first degree relatives of type-2 diabetes mellitus patients: A prospective study in north Indian population

A total of 172 first degree relatives (FDRs) and 178 controls were included in this study. All the cases and controls were subjected to various anthropometric measurements, fasting and postprandial glucose estimation, fasting insulin measurement and fasting lipid profile. Results revealed the prevalence of Impaired Fasting Glucose (IFG) (cases 37% Vs controls 11.6%), Impaired Glucose Tolerance (IGT) (cases 34.3% Vs controls 11.2%) and diabetes (cases 11.05% controls 3.37%) was significantly higher in first degree relatives. Insulin resistance was measured using various methods, which included fasting plasma insulin (FPI), Homeostasis Model Assessment for Insulin Resistance (HOMA_IR), insulin sensitivity index (ISI) (Mffm/l). Prevalence of insulin resistance (Insulin Resistance) as observed comparing FPI and HOMA_IR in cases and controls was 43.6% and 11.24% (P=0.005) and 37.8% and 12.47% (P=0.000) respectively. Prevalence of IR (Insulin Resistance) observed in cases having Normal Glucose Tolerance (NGT), Impaired Fasting Glucose (IFG), Impaired Glucose Tolerance (IGT) and diabetes mellitus measuring FPI Vs HOMA_IR was 37.5% vs 30.2%, 45% vs 40%, 38.98% vs 37.28% and 36.84% vs 31.57% as accordingly. However, ISI (Mffm/l) was not found to be a promising index for IR due to its poor specificity. Though HOMA is taken as gold standard for measurement of IR globally, our study observed fasting plasma insulin representing high sensitivity (89.7%) and specificity (93.3%) as compared to HOMA. Thus FPI had emerged in this work as a simple and reliable test for diagnosing insulin resistance across the population susceptible to develop diabetes including FDRs.     

Cord Blood Insulin Levels: It’s Correlation with Gender,Birth Weight and Placental Weight in Term Newborns

The cause of more insulin resistance in female than males are still unknown. To know the cause from early life, normal values of relevant parameters are required. So, aim of this study was to determine the reference levels of glucose and insulin in cord blood of term newborns and to examine their effects on gender, placental and birth weight of term newborns. In cross sectional study 60 consecutive term newborns were included from constituent hospitals. Placental and birth weights were measured and cord blood was collected for estimation of serum insulin and plasma glucose. Plasma glucose estimation was done by auto analyzer (GOD–POD method) and serum insulin analysis was done using Insulin ELISA Kit. After analysis, mean ± 2SD used for estimating cord blood insulin and glucose levels, which were 10.1 ± 7.8 μIU/mL and 67.8 ± 33.8 mg/dL respectively. Correlation of insulin with both birth weight and placental weight were r = 0.359 and 0.41 respectively; p < 0.001. Interestingly we found higher insulin levels in females as compared to male newborns in spite of having lower birth weight in them. In conclusion this study reported the levels of insulin and glucose in cord blood of term newborns. Incidentally, this is the first study as per our knowledge to report significant correlation between cord blood insulin, glucose with birth weight, placental weight and gender in south India. Female newborns had higher insulin levels than males, despite lesser birth weight can be attributed to intrinsic insulin resistance in them.