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Obesity induced insulin resistance is primarily regulated by the inhibitory phosphorylation of peroxisome proliferator-activated receptor γ at serine 273 (PPARγS273) which has been shown to be regulated by MEK and ERK. An upstream regulatory molecule of this pathway could be a therapeutic option. Here we analyzed the involvement of Fetuin-A (FetA), a key hepato-adipokine implicated in insulin resistance, as an upstream regulator molecule for the regulation of PPARγ inhibitory phosphorylation. Mice fed with standard diet (SD), high fat diet (HFD) and HFD with FetA knockdown (HFD-FetA KD ) were used to examine the role of FetA on PPARγS273 phosphorylation in adipocytes. The mechanism of regulation and its effect on skeletal muscle were studied using primary adipocytes, 3T3-L1 (preadipocyte) and C2C12 (myotube) cell lines. Increased FetA in HFD mice strongly correlated with augmentation of PPARγS273 phosphorylation in inflamed adipocytes while knockdown of FetA suppressed it. This effect of FetA was mediated through the activation of Ras which in turn activated MEK and ERK. On addressing how FetA could stimulate activation of Ras, we found that FetA triggered TNFα in inflamed adipocytes which induced Ras activation. The ensuing sharp fall in adiponectin level attenuated AMPK activation in skeletal muscle cells affecting mitochondrial ATP production. Our data reveal the essential role of FetA induced activation of Ras in regulating PPARγ inhibitory phosphorylation through Ras-MEK-ERK pathway which downregulates adiponectin disrupting skeletal muscle mitochondrial bioenergetics. Thus, FetA mediated PPARγ inactivation has adverse consequences upon adipocyte-myocyte crosstalk leading to disruption of energy homeostasis and loss of insulin sensitivity., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Accumulation and polarization of anti-inflammatory M2 to proinflammatory M1 macrophage in the adipose tissue of obese diabetic mice is an important pathogenic signature. It worsens lipid induced inflammation and insulin resistance. Here we demonstrate that a small molecule, a peroxyvanadate compound i.e. DmpzH [VO(O 2 ) 2 (dmpz)] or dmp, could robustly decrease macrophage infiltration, accumulation and their polarization in high fat diet (HFD) induced obese diabetic mice. In searching the underlying mechanism it was revealed that SIRT1 level was strikingly low in the inflamed adipose tissue of HFD mice as compared to mice fed with standard diet (SD). Administration of dmp markedly increased SIRT1 level by inducing its gene expression with a consequent decrease in macrophage population. Elevation of SIRT1 coincided with the decrease of MCP1, Fetuin-A (FetA) and IFNγ. Since MCP1 and FetA drive macrophage to inflamed adipose tissue and IFNγ promotes M2 to M1 transformation, both recruitment and M1 induced inflammation were found to be significantly repressed by dmp. In addressing the question about how dmp induced excess SIRT1 could reduce MCP1, FetA and IFNγ levels, we found that it was due to the inactivation of NFκB because of its deacetylation by SIRT1. Since NFκB is the transcriptional regulator of these molecules, their expressions were significantly suppressed and that caused sharp decline in macrophage recruitment and their polarity to M1. This effected a marked fall in proinflammatory cytokine level which significantly improved insulin sensitivity. dmp is likely to be the first molecule that rescues inflammatory burden contributed by macrophage in obese diabetic mice adipose tissue which causes significant increase in insulin sensitivity therefore it may be a meaningful choice to treat type 2 diabetes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Dramatic increase of diabetes over the globe is in tandem with the increase in insulin requirement. This is because destruction and dysfunction of pancreatic β-cells are of common occurrence in both Type1 diabetes and Type2 diabetes, and insulin injection becomes a compulsion. Because of several problems associated with insulin injection, orally active insulin mimetic compounds would be ideal substitute. Here we report a small molecule, a peroxyvanadate compound i.e. DmpzH[VO(O2)2(dmpz)], henceforth referred as dmp, which specifically binds to insulin receptor with considerable affinity (KD-1.17μM) thus activating insulin receptor tyrosine kinase and its downstream signaling molecules resulting increased uptake of [14C] 2 Deoxy-glucose. Oral administration of dmp to streptozotocin treated BALB/c mice lowers blood glucose level and markedly stimulates glucose and fatty acid uptake by skeletal muscle and adipose tissue respectively. In db/db mice, it greatly improves insulin sensitivity through excess expression of PPARγ and its target genes i.e. adiponectin, CD36 and aP2. Study on the underlying mechanism demonstrated that excess expression of Wnt3a decreased PPARγ whereas dmp suppression of Wnt3a gene increased PPARγ expression which subsequently augmented adiponectin. Increased production of adiponectin in db/db mice due to dmp effected lowering of circulatory TG and FFA levels, activates AMPK in skeletal muscle and this stimulates mitochondrial biogenesis and bioenergetics. Decrease of lipid load along with increased mitochondrial activity greatly improves energy homeostasis which has been found to be correlated with the increased insulin sensitivity. The results obtained with dmp, therefore, strongly indicate that dmp could be a potential candidate for insulin replacement therapy., Competing Interests: The authors have declared that no competing interests exist.

Aim: Asian Indians are believed to have a lower capacity to clear a glucose load even during normoglycemia. High post meal glucose levels have been linked to postprandial dyslipidemia and generation of proinflammatory cytokines. Since humans spend most of their time in the postprandial state, the present study aims to evaluate the relationship of insulin resistance (IR) in the basal state with dyslipidemia and systemic inflammation (hs-CRP, IL-6 and TNF-a), in the fasting state, 2h and 4h after a mixed meal, in Indian adults with normal glucose tolerance, and new onset type-2 diabetes., Methods: Forty-eight people with type 2 diabetes and 32 individuals with normoglycemia, 30-70 years age, not on medications, underwent blood sampling after overnight (12h) fast and 2 and 4h after a mixed meal (carbohydrates, proteins and fat content 79.1%, 7.7% and 13.2%, respectively)., Results: Triglyceride (TG), TG/HDL-C (high density lipoprotein), HDL-C/LDL-C (low density lipoprotein) ratios, IR parameters, and inflammatory markers were significantly higher among patients with diabetes. There was a fall in total cholesterol (TC), HDL-C and LDL-C at 2 and 4h after the meal in both groups. Compared with fasting, 4-h postprandial TC, TG and HDL-C were significantly better positively correlated with IR in normal individuals. Postprandial hs-CRP was not significantly different to fasting in both groups. Postprandial IL-6 and TNF-α were significantly lower in both groups., Conclusion: Consumption of a carbohydrate rich meal is associated with a rise in TG and fall in TC, HDL-C, LDL-C, IL-6 and TNF-α among normal individuals and people with type 2 diabetes., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Vitamin-D supplementation in vitamin-D insufficient/deficient prediabetes individuals is associated with significantly lower progression to diabetes (6/55 vs. 13/49; p=0.04) and higher reversal to normoglycemia (23/55 vs. 10/49; p=0.02), associated with decreased insulin resistance and systemic inflammation (TNFα and IL6). Baseline vitamin-D and 2h blood glucose independently predicted progression to diabetes., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background & Objectives: Patients with diabetes and vitamin-D insufficiency have increased insulin resistance. Similar observations among individuals with prediabetes are not well documented. The aim of this study was to find the occurrence of vitamin-D insufficiency/deficiency among individuals with prediabetes and to evaluate the relationship between vitamin-D status and insulin resistance., Methods: One hundred fifty seven individuals with prediabetes who fulfilled all the inclusion and exclusion criteria underwent clinical examination, anthropometric measurements (waist circumference, waist-hip ratio, waist-height ratio) and blood sampling after overnight fast for estimation of fasting blood glucose, fasting insulin, 25(OH)vitamin-D, intact parathyroid hormone (iPTH) and lipid profile. One hour post 75 g glucose (1hPG) blood glucose during oral glucose tolerance test was measured., Results: Vitamin-D deficiency/insufficiency was found in 115 (73.25%) individuals with prediabetes. Severe vitamin-D deficiency (<10 ng/ml) was seen in 14.65 per cent individuals. Individuals with the lowest vitamin-D levels (<10 ng/ml) had the highest insulin resistance (HOMA2-IR: 2.04 ± 0.67). Serum 25(OH)D had a statistically significant inverse correlation with insulin resistance (HOMA2-IR; r=-0.33; P=0.008), and positive correlation with insulin sensitivity (QUICKI; r=0.39; P=0.002), after adjusting for BMI and HbA1c. There was no correlation between vitamin-D status and estimated beta cell mass (HOMA-β). The mean waist-height ratio among individuals with prediabetes was 0.57 (normal<0.5) indicating a high risk of cardiovascular morbidity. Individuals with elevated 1hPG>155 mg/dl had significantly higher BMI and worse insulin resistance, and 1hPG correlated well with 2 hour post glucose blood glucose (r=0.57; P<0.001). INTERPRETATIONS & CONCLUSIONS: Vitamin-D deficiency/insufficiency may have some role in the development/worsening of insulin resistance in individuals with prediabetes in our country who have a high cardiovascular risk. Prospective studies on a large group of individuals need to be done to confirm the findings.

Syndrome of extreme insulin resistance (SEIR) is a rare spectrum disorder with a primary defect in insulin receptor signalling, noted primarily in children, and is often difficult to diagnose due to the clinical heterogeneity.SEIR was diagnosed in an adolescent girl with facial dysmorphism,exuberant scalp and body hair, severe acanthosis, lipoatrophy, dental abnormalities, and short stature (Rabson-Mendenhall phenotype). She had elevated fasting (422.95 pmol/L) and post-glucose insulin levels(>2083 pmol/L). Total body fat was decreased (11%; dual-energy X-ray absorptiometry). Basal growth hormone (GH) was increased (7.9 μg/L)with normal insuline-like growth factor 1 (37.6 nmol/L) suggestive of GH resistance. She had fatty liver and polycystic ovaries. Echocardiography revealed ostium secundum type atrial septal defect (ASD). Blood glucose normalized with pioglitazone (30 mg/day). Delayed development, severe insulin resistance, mild hyperglycemia, absence of ketosis, and remarkable response of hyperinsulinemia and hyperglycemia to pioglitazone which persisted even after 1 year of diagnosis are some of the notable features of this patient. This is perhaps the first report of occurrence of congenital heart disease (ASD) in a patient of SEIR (Rabson-Mendenhall phenotype). This report highlights the clinical features of SEIR and the role of insulin sensitizers like pioglitazone in the management of such patients.

Toll-like receptor 4 (TLR4) has a key role in innate immunity by activating an inflammatory signaling pathway. Free fatty acids (FFAs) stimulate adipose tissue inflammation through the TLR4 pathway, resulting in insulin resistance. However, current evidence suggests that FFAs do not directly bind to TLR4, but an endogenous ligand for TLR4 remains to be identified. Here we show that fetuin-A (FetA) could be this endogenous ligand and that it has a crucial role in regulating insulin sensitivity via Tlr4 signaling in mice. FetA (officially known as Ahsg) knockdown in mice with insulin resistance caused by a high-fat diet (HFD) resulted in downregulation of Tlr4-mediated inflammatory signaling in adipose tissue, whereas selective administration of FetA induced inflammatory signaling and insulin resistance. FFA-induced proinflammatory cytokine expression in adipocytes occurred only in the presence of both FetA and Tlr4; removing either of them prevented FFA-induced insulin resistance. We further found that FetA, through its terminal galactoside moiety, directly binds the residues of Leu100-Gly123 and Thr493-Thr516 in Tlr4. FFAs did not produce insulin resistance in adipocytes with mutated Tlr4 or galactoside-cleaved FetA. Taken together, our results suggest that FetA fulfills the requirement of an endogenous ligand for TLR4 through which lipids induce insulin resistance. This may position FetA as a new therapeutic target for managing insulin resistance and type 2 diabetes.

Fetuin-A, a hepatic secretory protein, has recently been implicated in insulin resistance and Type 2 diabetes. It is an endogenous inhibitor of insulin receptor tyrosine kinase. However, regulation of fetuin-A synthesis in relation to insulin resistance is unclear. In the present paper, we report that both non-esterified ('free') fatty acids and fetuin-A coexist at high levels in the serum of db/db mice, indicating an association between them. For an in-depth study, we incubated palmitate with HepG2 cells and rat primary hepatocytes, and found enhanced fetuin-A secretion to more than 4-fold over the control. Interestingly, cell lysates from these incubations showed overexpression and activity of NF-kappaB (nuclear factor kappaB). In NF-kappaB-knockout HepG2 cells, palmitate failed to increase fetuin-A secretion, whereas forced expression of NF-kappaB released fetuin-A massively in the absence of palmitate. Moreover, palmitate stimulated NF-kappaB binding to the fetuin-A promoter resulting in increased reporter activity. These results suggest NF-kappaB to be the mediator of the palmitate effect. Palmitate-induced robust expression of fetuin-A indicates the occurrence of additional targets, and we found that fetuin-A severely impaired adipocyte function leading to insulin resistance. Our results reveal a new dimension of lipid-induced insulin resistance and open another contemporary target for therapeutic intervention in Type 2 diabetes.

Background and Aims: The predictive potential of neck circumference (NC) based indices (a measure of upper body fat distribution) for predicting metabolic syndrome (MetS) and its components among Indians is not known. This study aimed to evaluate the role of NC and neck height ratio (NHtR) as independent predictors of MetS and its components as compared to traditional anthropometric indices. Materials and Methods: A total of 451 individuals from 867 screened individuals, 30–80 years age, without any co-morbid state who gave informed written consent underwent clinical, anthropometric, and biochemical assessment. Results: Patients with MetS in both the sexes had significantly higher NC, NHtR, glycated hemoglobin, fasting glucose, and dyslipidemia (higher triglycerides, total cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio, low-density lipoprotein cholesterol/HDL-C ratio, and lower HDL-C). In both sexes, individuals in the highest tertile of NC had significantly greater central and generalized obesity, lower HDL-C, and significantly higher MetS. Receiver operating characteristic analysis revealed waist circumference (WC) to have the largest area under the curve for predicting MetS in both sexes, followed by NHtR, NC, and body mass index. NC and NHtR of >34.9 cm (sensitivity 78.6%; specificity 59.3%) and >21.17 cm/m (sensitivity 80.7% and specificity 64.6%) respectively for men and >31.25 cm (sensitivity 72.3%; specificity 64.4%) and >20.48 cm/m (sensitivity 80.4% and specificity 60%) respectively for women were the best values for identifying MetS. Increased NC and NHtR had odds ratio of 1.52 (95% confidence interval [CI]: 1.37–1.68; P< 0.001) and 1.96 (95% CI: 1.67–2.29; P< 0.001) respectively in identifying MetS. Conclusion: NC and NHtR are good predictors of MetS and cardiovascular risk factors in Asian Indians. NHtR is reliable and perhaps an even better index than NC with regards to cardiovascular risk prediction. [ABSTRACT FROM AUTHOR]

In obese individuals, visceral adipose tissue (VAT) is the seat of chronic low-grade inflammation (metaflammation), but the mechanistic link between increased adiposity and metaflammation largely remains unclear. In obese individuals, deregulation of a specific adipokine, chemerin, contributes to innate initiation of metaflammation by recruiting circulating plasmacytoid dendritic cells (pDCs) into VAT through chemokine-like receptor 1 (CMKLR1). Adipose tissue-derived high-mobility group B1 (HMGB1) protein activates Toll-like receptor 9 (TLR9) in the adipose-recruited pDCs by transporting extracellular DNA through receptor for advanced glycation end products (RAGE) and induces production of type I interferons (IFNs). Type I IFNs in turn help in proinflammatory polarization of adipose-resident macrophages. IFN signature gene expression in VAT correlates with both adipose tissue and systemic insulin resistance (IR) in obese individuals, which is represented by ADIPO-IR and HOMA2-IR, respectively, and defines two subgroups with different susceptibility to IR. Thus, this study reveals a pathway that drives adipose tissue inflammation and consequent IR in obesity. [ABSTRACT FROM AUTHOR]

Backgrounds/Aims: The lipid induced insulin resistance is a major pathophysiologic mechanism underlying glucose intolerance of varying severity. PPARα-agonists are proven as effective hypolipidemic agents. The aim of this study was to see if impaired glucose uptake in palmitate treated myotubes is reversed by fenofibrate. Methods: Palmitate-treated myotubes were used as a model for insulin resistance, impaired glucose uptake, fatty acid oxidation and ceramide synthesis. mRNA levels of CPT1 and CPT2 were determined by PCR array and Q-PCR. Results: The incubation of myotubes with 750 uM palmitate not only reduced glucose uptake but also impaired fatty acid oxidation and cytosolic ceramide accumulation. Palmitate upregulated CPT1b expression in L6 myotubes, while CPT2 expression level remained unchanged. The altered stoichiometric ratio between the two CPT isoforms led to reduced fatty acid oxidation (FAO), ceramide accumulation and impaired glucose uptake, whereas administration of 200 µM fenofibrate signifcantly reversed the above abnormalities by increasing CPT2 mRNA levels and restoring CPT1b to CPT2 ratio. Conclusion: Palmitate-induced alteration in the stoichiometric ratio of mitochondrial CPT isoforms leads to incomplete FAO and enhanced cytosolic ceramide accumulation that lead to insulin resistance. Fenofibrate ameliorated insulin resistance by restoring the altered stoichiometry by upregulating CPT2 and preventing, cytoplasmic ceramide accumulation. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hirsuitism though not uncommon (24%), is not considered to be a prominent feature of acromegaly because of its lack of specificity and occurrence. Hirsuitism is very common in women of reproductive age (5-7%) and has been classically associated with polycystic ovarian syndrome (PCOS). Twenty-eight year lady with 3 year duration of hirsuitism (Modified Ferriman Gallwey score-24/36 ), features of insulin resistance (acanthosis), subtle features of acromegaloidism (woody nose and bulbous lips) was diagnosed to have acromegaly in view of elevated IGF-1 (1344 ng/ml; normal: 116-358 ng/ml), basal (45.1 ng/ml) and post glucose growth hormone (39.94 ng/ml) and MRI brain showing pituitary macroadenoma. Very high serum androstenedione (>10 ng/ml; normal 0.5-3.5 ng/ml), elevated testosterone (0.91 ng/ml, normal <0.8) and normal dehydroepiandrosterone sulphate (DHEAS) (284 mcg/dl, normal 35-430 mcg/dl) along with polycystic ovaries on ultrasonography lead to diagnosis of associated PCOS. She was also diagnosed to have diabetes. This case presentation intends to highlight that hirsuitism may rarely be the only prominent feature of acromegaly. A lookout for subtle features of acromegaly in all patients with hirsuitism and going for biochemical evaluation (even at the risk of investigating many patients of insulin resistance and acromegloidism) may help us pick up more patients of acromegaly at an earlier stage thus help in reducing disease morbidity. [ABSTRACT FROM AUTHOR]

Although several reports demonstrated that accumulation of excess lipid in adipose tissue produces defects in adipocyte which leads to the disruption of energy homeostasis causing severe metabolic problems, underlying mechanism of this event remains yet unclear. Here we demonstrate that FetuinA (FetA) plays a critical role in the impairment of two metabolic sensors, SIRT1 and AMPK, in inflamed adipocytes of high fat diet (HFD) mice. A linear increase in adipocyte hypertrophy from 10 to 16 week was in tandem with the increase in FetA and that coincided with SIRT1 cleavage and decrease in pAMPK which adversely affects PGC1α activation. Knock down (KD) of FetA gene in HFD mice could significantly improve this situation indicating FetA's contribution in the damage of energy sensors in inflamed adipocyte. However, FetA effect was not direct, it was mediated through TNF-α which again is dependent on FetA as FetA augments TNF-α expression. FetA being an upstream regulator of TNF-α, its suppression prevented TNF-α mediated Caspase-1 activation and cleavage of SIRT1. FetA induced inactivation of PGC1α due to SIRT1 cleavage decreased PPARϒ, adiponectin, NRF1 and Tfam expression. All these together caused a significant fall in mitochondrial biogenesis and bioenergetics that disrupted energy homeostasis resulting loss of insulin sensitivity. Taken together, our findings revealed a new dimension of FetA, it not only induced inflammation in adipocyte but also acts as an upstream regulator of SIRT1 cleavage and AMPK activation. Intervention of FetA may be worthwhile to prevent metabolic imbalance that causes insulin resistance and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Adiponectin secreted from adipocytes is an anti-diabetic and anti-atherogenic adipokine. Adiponectin level is known to fall significantly in obesity induced type 2 diabetes which worsen insulin sensitivity because of aberrant lipid management. However, underlying mechanism of adiponectin decrease in obese diabetic condition is yet unclear. We report here that lowering of plasma adiponectin coincided with the higher Fetuin A (FetA) level in high fat diet (HFD) induced obese diabetic mice. Knock down of FetA gene (FetA KD ) elevated adiponectin level markedly in HFD mice, while reinforcement of FetA into FetA KD HFD mice reduced its level again. These results indicate FetA's involvement in the lowering of adiponectin level in obesity induced diabetic mice. Our findings to understand how FetA could affect adiponectin decrease demonstrated that FetA could enhance Wnt3a expression in the adipocyte of HFD mice. FetA addition to 3T3L1 adipocyte incubation elevated Wnt3a expression in a dose dependent manner. Overexpression of Wnt3a by FetA inhibited PPARγ and adiponectin. FetA failed to reduce PPARγ and adiponectin in Wnt3a gene knocked down 3T3L1` adipocytes. All these suggest that FetA mediate its inhibitory effect on adiponectin through Wnt3a–PPARγ pathway. Inhibition of adiponectin expression through FetA and Wnt3a significantly compromised with the activation of AMPK and its downstream signalling molecules which adversely affected lipid management causing loss of insulin sensitivity. Downregulation of adiponectin in inflamed adipocyte by FetA through the mediation of Wnt3a and PPARγ is a new report. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of circulating FFA leads to intra-myocellular lipid accumulation that induces mitochondrial ROS generation and worsens IR. However, the molecular mechanisms behind are unclear. We identified thioredoxin interacting protein (TxNIP), which is overexpressed in T2DM, to be a promoter of ROS-induced IR. We observed upregulation of TxNIP upon palmitate treatment in skeletal muscle cells that led to ROS generation and Glut-4 downregulation resulting in impaired glucose-uptake. FFA-induced overexpression of TxNIP gene was mediated through the activation of its bona-fide trans activator, ChREBP. Further, Palmitate-induced impairment in AMPK-SIRT-1 pathway resulted in overexpression of ChREBP. While Fenofibrate, abrogated PA-induced TxNIP expression and ROS generation in skeletal muscle cells, Saroglitazar, a dual PPARα/γ-agonist, not only inhibited PA-induced TXNIP expression but also led to greater improvement in glucose uptake. Taken together, TxNIP appears to be an important factor in FFA-induced ROS generation and IR in skeletal muscle cells, which can be modulated for the management of this complex disorder. [ABSTRACT FROM AUTHOR]

Macrophage infiltration into adipose tissue during obesity and their phenotypic conversion from anti-inflammatory M2 to proinflammatory M1 subtype significantly contributes to develop a link between inflammation and insulin resistance; signaling molecule(s) for these events, however, remains poorly understood. We demonstrate here that excess lipid in the adipose tissue environment may trigger one such signal. Adipose tissue from obese diabetic db/db mice, high fat diet-fed mice, and obese diabetic patients showed significantly elevated fetuin-A (FetA) levels in respect to their controls; partially hepatectomized high fat diet mice did not show noticeable alteration, indicating adipose tissue to be the source of this alteration. In adipocytes, fatty acid induces FetA gene and protein expressions, resulting in its copious release. We found that FetA could act as a chemoattractant for macrophages. To simulate lipid-induced inflammatory conditions when proinflammatory adipose tissue and macrophages create a niche of an altered microenvironment, we set up a transculture system of macrophages and adipocytes; the addition of fatty acid to adipocytes released FetA into the medium, which polarized M2 macrophages to M1. This was further confirmed by direct FetA addition to macrophages. Taken together, lipid-induced FetA from adipocytes is an efficient chemokine for macrophage migration and polarization. These findings open a new dimension for understanding obesity-induced inflammation. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Serum Vitamin-D Predicts Insulin Resistance in Individuals With Prediabetes," in the 2013 issue is presented.

A response from the authors of the article "Serum Vitamin-D Predicts Insulin Resistance in Individuals With Prediabetes," in the 2013 issue is presented.

Abstract: Prediabetes (IPD; n =122) and normoglycemic individuals (n =100) underwent assessment of polymorphisms of TNFα (−238, −308) and IL6 (−174). After 27.25±5.64 months, 16 IPD had reverted to normoglycemia and 18 progressed to diabetes. TNFα −238AA/GA genotypes were significantly more common in IPD, had higher TNFα, higher progression to diabetes and lower reversal. [Copyright &y& Elsevier]