Relationship between modified homeostasis model assessment/correlative serum factors and diabetic retinopathy among type 2 diabetics with insulin therapy in Guangzhou, China

AIM:To explore the related risk factors for diabetic retinopathy(DR)in type 2 diabetes with insulin therapy.METHODS:We studied the relationships among blood glucose,serum C-peptide,plasma insulin,beta-cell function and the development of DR.Beta-cell function was assessed by a modified homeostasis model assessment(modified HOMA)which was gained by using C-peptide to replace insulin in the homeostasis model assessment(HOMA)of beta-cell function.We also studied the relationships between modified HOMA index and serum C-peptide response to 100 g tasteless steamed bread to determine the accuracy of modified HOMA.RESULTS:Our study group consisted of 170 type 2diabetic inpatients with DR(age:58.35±13.87y,mean±SD)and 205 type 2 diabetic inpatients with no DR(NDR)(age:65.52±11.59y).DR patients had higher age,longer diabetic duration,higher hypertension grade,higher postprandial plasma glucose,higher fluctuation level of plasma glucose,lower body mass index(BMI),lower postprandial serum insulin and C-peptide,lower fluctuation level of serum insulin and C-peptide(P【0.05).In our logistic regression model,duration of diabetes,hypertension grade,fasting plasma insulin and glycosylated hemoglobin(HbA1C)were significantly associated with the presence of DR after adjustment for confounding factors(P【0.05).CONCLUSION:Our results suggested although modified HOMA showed significant correlation to the occurrence of DR on Spearman’s rank-correlationanalysis,logistic regression showed no significant association between these two variables after adjustment for relevant confounding factors(such as age,sex,duration of diabetes,BMI,hypertension grade,HbA1C,plasma insulin).Duration of diabetes,hypertension grade,fasting plasma insulin and HbA1C were independently associated with the development of DR in Chinese type 2 diabetics.

Hepatitis C virus induced insulin resistance impairs response to anti viral therapy

Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (HCC). The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-α (TNF-α) and suppressor of cytokine signaling 3 (SOC-3). IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis and even HCC. In addition, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon.

Wrist circumference: A new marker for insulin resistance in African women with polycystic ovary syndrome

BACKGROUND Insulin resistance(IR)is the main complication found in 35%-80%of women with polycystic ovary syndrome(PCOS).However,there is no definite consensus regarding which marker to use for its assessment in PCOS women.Research has shown that hyperinsulinemia is correlated with increased bone mass.Given that most women with PCOS are insulin resistant,which is independent from body fat and characterized by hyperinsulinemia,it could be hypothesized that there would be an increased bone mass in the patient as a result.Subsequently,increased bone mass could be measured using the wrist circumference method.AIM To assess the wrist circumference as an easy-to-detect marker of IR in Congolese women with PCOS.METHODS Seventy-two Congolese women with PCOS and seventy-one controls from the same ethnic group,were enrolled in the study(mean age 24.33±5.36 years).Fasting biochemical parameters,and the Homeostasis Model Assessment of insulin resistance(HOMA-IR)and body composition were evaluated.The nondominant wrist circumference was measured manually,as was the waist circumference(WC),hip circumference,height and weight.Calculated measures included evaluation of body mass index(BMI),Waist-to-Height(WHtR)and Waist-to-hip ratio(WHR).In addition,body composition was assessed by Bioelectrical Impedance Analysis using a body fat analyzer.RESULTS The non-dominant wrist circumference was more closely correlated with HOMAIR(r=0.346;P=0.003)and was the best anthropometrical marker correlated with IR(P=0.011)compared with other anthropometrical markers in women with PCOS:Dominant Wrist Circumference(r=0.315;P=0.007),Waist Circumference(WC)(r=0.259;P=0.028),BMI(r=0.285;P=0.016),WHR(r=0.216;P=0,068)and WHtR(r=0.263;P=0.027).The diagnostic accuracy of the non-dominant wrist circumference for the presence or absence of IR using Receiver-operating characteristic(ROC)curve analysis showed that the area under the ROC curve was 0.72.A cutoff value for the non-dominant wrist circumference of 16.3 cm was found to be the best predictor of IR in Congolese women with PCOS.CONCLUSION Non-dominant wrist circumference is,to date,the best anthropometrical marker of IR in Sub-Saharan African women with PCOS.It could be suggested as an easy-to-detect marker for assessing IR.

Nonalcoholic steatohepatitis and insulin resistance in children

Various pathological conditions can cause fatty liver in children. Nonalcoholic steatohepatitis(NASH) in children has been known since 1983. However, NASH diagnosed in childhood does not have a favorable outcome.The pathological characteristics of NASH are significantly different between children and adults. Nonalcoholic fatty liver disease(NAFLD)/NASH is accompanied by insulin resistance, which plays a pivotal role in its pathophysiology in both children and adults. In NASH,a "two-hit" model involving triglyceride accumulation(first hit) and liver damage(second hit) has been accepted. Insulin resistance was found to correlate with changes in fat levels; however, it did not correlate with fibrosis or NAFLD activity score in children. Therefore,insulin resistance may be important in the first hit.Because there is obvious familial clustering in NASH,genetic predisposition as well as environmental factors including diet might be the second hit of NAFLD/NASH.

Effectiveness and safety of human umbilical cord-mesenchymal stem cells for treating type 2 diabetes mellitus

BACKGROUND Progressive pancreaticβ-cell dysfunction is a fundamental part of the pathology of type 2 diabetes mellitus(T2DM).Cellular therapies offer novel opportunities for the treatment of T2DM to improve the function of isletβ-cells.AIM To evaluate the effectiveness and safety of human umbilical cord-mesenchymal stem cell(hUC-MSC)infusion in T2DM treatment.METHODS Sixteen patients were enrolled and received 1×10^(6) cells/kg per week for 3 wk as intravenous hUC-MSC infusion.The effectiveness was evaluated by assessing fasting blood glucose,C-peptide,normal glycosylated hemoglobin A1c(HbA1c),insulin resistance index(homeostatic model assessment for insulin resistance),and isletβ-cell function(homeostasis model assessment ofβ-cell function).The dosage of hypoglycemic agents and safety were evaluated by monitoring the occurrence of any adverse events(AEs).RESULTS During the entire intervention period,the fasting plasma glucose level was significantly reduced[baseline:9.3400(8.3575,11.7725),day 14±3:6.5200(5.2200,8.6900);P<0.01].The HbA1c level was significantly reduced on day 84±3[baseline:7.8000(7.5250,8.6750),day 84±3:7.150(6.600,7.925);P<0.01].The patients’isletβ-cell function was significantly improved on day 28±3 of intervention[baseline:29.90(16.43,37.40),day 28±3:40.97(19.27,56.36);P<0.01].The dosage of hypoglycemic agents was reduced in all patients,of whom 6(50%)had a decrement of more than 50%and 1(6.25%)discontinued the hypoglycemic agents.Four patients had transient fever,which occurred within 24 h after the second or third infusion.One patient(2.08%)had asymptomatic nocturnal hypoglycemia after infusion on day 28±3.No liver damage or other side effects were reported.CONCLUSION The results of this study suggest that hUC-MSC infusion can improve glycemia,restore isletβ-cell function,and reduce the dosage of hypoglycemic agents without serious AEs.Thus,hUC-MSC infusion may be a novel option for the treatment of T2DM.

Insulin resistance and hepatitis C

Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients. Hepatitis C virus （HCV） infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine （SOC-3）; both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients＇. ＂viral＂ and ＂metabolic＂ insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include： （1） steatosis, （2） hyperleptinemia, （3） increased TNF production, （4） impaired expression of PPARy receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American. Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin. Indeed, in genotype 1, the sustained response rate was twice （60%） in patients with HOMA ≤ 2 than patients with HOMA 〉 2. In experiments carried out on Huh-7 cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin （at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state） was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance, steatosis and fibrosis progression.

Effects of intermittent fasting on health markers in those with type 2 diabetes:A pilot study

AIMTo determine the short-term biochemical effects and clinical tolerability of intermittent fasting (IF) in adults with type 2 diabetes mellitus (T2DM).METHODSWe describe a three-phase observational study (baseline 2 wk, intervention 2 wk, follow-up 2 wk) designed to determine the clinical, biochemical, and tolerability of IF in community-dwelling volunteer adults with T2DM. Biochemical, anthropometric, and physical activity measurements (using the Yale Physical Activity Survey) were taken at the end of each phase. Participants reported morning, afternoon and evening self-monitored blood glucose (SMBG) and fasting duration on a daily basis throughout all study stages, in addition to completing a remote food photography diary three times within each study phase. Fasting blood samples were collected on the final days of each study phase.RESULTSAt baseline, the ten participants had a confirmed diagnosis of T2DM and were all taking metformin, and on average were obese [mean body mass index (BMI) 36.90 kg/m2]. We report here that a short-term period of IF in a small group of individuals with T2DM led to significant group decreases in weight (-1.395 kg, P = 0.009), BMI (-0.517, P = 0.013), and at-target morning glucose (SMBG). Although not a study requirement, all participants preferentially chose eating hours starting in the midafternoon. There was a significant increase (P < 0.001) in daily hours fasted in the IF phase (+5.22 h), although few attained the 18-20 h fasting goal (mean 16.82 ± 1.18). The increased fasting duration improved at-goal (< 7.0 mmol/L) morning SMBG to 34.1%, from a baseline of 13.8%. Ordinal Logistic Regression models revealed a positive relationship between the increase in hours fasted and fasting glucose reaching target values (χ2 likelihood ratio = 8.36, P = 0.004) but not for afternoon or evening SMBG (all P > 0.1). Postprandial SMBGs were also improved during the IF phase, with 60.5% readings below 9.05 mmol/L, compared to 52.6% at baseline, and with less glucose variation. Neither insulin resistance (HOMA-IR), nor inflammatory markers (C-reactive protein) normalized during the IF phase. IF led to an overall spontaneous decrease in caloric intake as measured by food photography (Remote Food Photography Method). The data demonstrated discernable trends during IF for lower energy, carbohydrate, and fat intake when compared to baseline. Physical activity, collected by a standardized measurement tool (Yale Physical Activity Survey), increased during the intervention phase and subsequently decreased in the follow-up phase. IF was well tolerated in the majority of individuals with 6/10 participants stating they would continue with the IF regimen after the completion of the study, in a full or modified capacity (i.e., every other day or reduced fasting hours).CONCLUSIONThe results from this pilot study indicate that short-term daily IF may be a safe, tolerable, dietary intervention in T2DM patients that may improve key outcomes including body weight, fasting glucose and postprandial variability. These findings should be viewed as exploratory, and a larger, longer study is necessary to corroborate these findings.

Effects of nasal continuous positive airway pressure treatment on insulin resistance and ghrelin levels in non-diabetic apnoeic patients with coronary heart disease

Background Obesity is a common risk factor for several diseases. Obesity related hormone and increased insulin resistance （IR） may contribute to the effects of obstructive sleep apnoea on cardiovascular consequences. We investigated ghrelin and IR in non-diabetic apnoeic patients with stable coronary heart disease and assessed the effects of continuous positive airway pressure （CPAP）. Methods Plasma ghrelin, glucose and insulin were measured in 22 patients with CPAP and 22 matched controls without CPAP at baseline and three months. Indexes including homeostasis model assessment IR （HOMA IR）, HOMA S and HOMA β were calculated for the assessment of IR, insulin sensitivity and pancreatic β cell function. Results At three months follow-up, plasma ghrelin levels and HOMA IR in CPAP group were significantly decreased （P=0.002 and 0.046, respectively） while those in control group increased significantly （P=0.012 and 0.009, respectively）. Significant moderate correlations were found between ghrelin vs. HOMA IR and ghrelin vs. HOMA S after CPAP, however, for those without CPAP, no significant associations were observed. Conclusions Short-term effective continuous positive airway pressure had a significant effect on lowering plasma ghrelin levels and IR, but not body fat. Further large scale and longer term studies are warranted to corroborate these findings.