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Background No data are available on the association between dietary insulin index (DII) and dietary insulin load (DIL) and the risk of breast cancer (BC). Patients and Methods This hospital-based case–control study enrolled 150 newly diagnosed cases of BC and 150 age-matched controls. All cases were patients with pathologically confirmed BC, with no history of any type of other pathologically confirmed cancers. Controls were selected from visitors, relatives, and friends of non-cancer patients in other wards who had no family relationships with the cases. We assessed the dietary intakes of study participants using a validated 147-item semiquantitative food frequency questionnaire. DII and DIL were obtained from previously published data. Results A significant positive association was found between DII and BC (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.02-3.25), such that after considering energy intake and age, participants in the highest tertile of DII had 1.86 times greater risk of BC than those in the lowest tertile (OR, 1.86; 95% CI, 1.03-3.35). However, this association became non-significant after controlling for further potential risk factors (OR, 3.26; 95% CI, 0.9-11.7). Furthermore, we observed a significant positive association between DIL and BC (OR, 1.9; 95% CI, 1.06-3.40). The association remained significant even after controlling for age and energy intake. Further controlling for other potential confounders resulted in the disappearance of the association (OR, 3.06; 95% CI, 0.87-10.6). Conclusion Adherence to a diet with high DII and DIL was not associated with odds of BC after controlling for potential confounders.

The progression of cardiometabolic diseases is determined by both genetic and environmental factors. Gene–diet interactions may therefore be important in modulating the risks of developing metabolic diseases. The objectives were to investigate the effect of the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms and dietary insulin index (DII) and dietary insulin load (DIL) on cardiometabolic markers among diabetic patients. In this cross-sectional study, blood samples were collected from 667 patients. DIL and DII were defined using a validated FFQ. Genotyping the BDNF Val66Met polymorphism was conducted by the PCR-Restriction fragment length polymorphism (RFLP) method. Interactions between dietary indices and gene variants were evaluated using a generalised linear model. PGF2a concentrations were significantly higher among Val homozygotes than Met-allele carrier. This study revealed that, compared with individuals with the Val/Val genotype, those with the Met/Val or Met/Met genotype had lower BMI (Pinteraction = 0·04), TAG (Pinteraction = 0·04), leptin (Pinteraction = 0·01), LDL (Pinteraction = 0·04) and total cholesterol (Pinteraction = 0·01) when they consumed diets higher on the DIL index. Moreover, the highest quartile of the DIL, compared with the lowest, showed increase in waist circumference (Pinteraction = 0·02) and LDL/HDL (Pinteraction = 0·04) for Val/Val homozygotes compared with Met-allele carriers. BDNF Val66Met variants may interact with DIL and DII, thus be involved in the development of cardiometabolic risk factors. If diabetic patients with Met alleles regulate dietary intakes, they have a protective opportunity to regulate their cardiometabolic markers.

Gene–diet interactions may play an important role in the inter individual diversity observed in on cardiovascular disease (CVD) risk factors. Therefore, in the current study, we examined the interaction of CETP TaqB1 polymorphism with dietary insulin index and load (DII and DIL), in altering on CVD risk factors among type 2 diabetes mellitus (T2DM). In this cross-sectional study, blood samples were collected from 220 type 2 diabetic patients (134 females and 86 male) with a mean age of 52.24 years in Tehran, Iran. DIL and DII were obtained via validated food-frequency questionnaire (FFQ). Taq1B polymorphism was genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Biochemical markers including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), superoxide dismutase (SOD), C-reactive protein (CRP), total antioxidant capacity (TAC), pentraxin-3 (PTX3), isoprostaneF2α (PGF2α). interleukin 18 (IL18), leptin and ghrelin were measured by standard protocol. Patients with B1B1 genotype had lower lipid profiles include LDL/HDL (P

Summary Background & aims It is believed that diets high in glycemic index (GI), glycemic load (GL), Insulin index (II), and Insulin load (IL) are associated with the increased risks of certain cancers through increasing serum glucose or insulin levels. Methods We conducted this systematic review of cohort studies to evaluate the possible relation between GI, GL, II, and IL with diabetes-related cancers, including colorectal, bladder, breast, endometrium, liver, pancreas, and prostate cancers. Two separate investigators conducted a literature search through PubMed/Medline, Scopus, and Web of Science databases up to February 2020, plus reference lists of relevant articles. Results Fifty-three cohort studies with a total of 100 098 cancer cases were included in this systematic review. Fifteen out of eighteen studies among breast cancer cases reported no significant association between GI/GL and cancer risk. These numbers were 4 out of 13 for colorectal cancer, 7 out of 9 for endometrial cancer, 2 out of 3 for liver cancer, 8 out of 10 for pancreatic cancer, and 3 out of 3 for prostate cancer. Only one cohort investigated this association in terms of bladder cancer and reported a significant association. Also, five studies reported this relation in terms of II/IL, and only one cohort among endometrial cancer patients observed a significant positive association between the risk of cancer and IL. Conclusion We concluded a weak association between dietary GI/GL and no association between II/IL with diabetes-related cancer risk. More cohort studies are required to be performed regarding II/IL and the risk of cancer.

Background: We investigated the associations of postdiagnostic dietary glycemic index (GI), glycemic load (GL), insulin index (II), and insulin load (IL) with breast cancer–specific and all-cause mortality. Methods: Among 8,932 women with stage I–III breast cancer identified in the Nurses' Health Study (NHS; 1980–2010) and NHSII (1991–2011), we prospectively evaluated the associations between postdiagnostic GI, GL, II, and IL, and breast cancer–specific and all-cause mortality. Participants completed a validated food frequency questionnaire every 4 years after diagnosis. Results: During follow-up by 2014 in the NHS and 2015 in the NHSII, 2,523 deaths, including 1,071 from breast cancer, were documented. Higher postdiagnostic GL was associated with higher risk of both breast cancer–specific mortality [HRQ5vsQ1 = 1.33; 95% confidence interval (CI) = 1.09–1.63; Ptrend = 0.008] and all-cause mortality (HRQ5vsQ1 = 1.26; 95% CI = 1.10–1.45; Ptrend = 0.0006). Higher all-cause mortality was also observed with higher postdiagnostic GI (HRQ5vsQ1 = 1.23; 95% CI = 1.08–1.40; Ptrend = 0.001), II (HRQ5vsQ1 = 1.20; 95% CI = 1.04–1.38; Ptrend = 0.005), and IL (HRQ5vsQ1 = 1.23; 95% CI = 1.07–1.42; Ptrend = 0.0003). The associations were not modified by insulin receptor or estrogen receptor status of the tumor, or body mass index. Conclusions: We found that higher dietary GL, reflecting postprandial glucose response, after a breast cancer diagnosis was associated with higher risk of breast cancer–specific mortality. Higher dietary GI, GL, II, and IL after a breast cancer diagnosis were associated with higher risk of death from any cause. Impact: These results suggest that carbohydrate quantity and quality may be important in breast cancer prognosis. See related commentary by McTiernan, p. 252

Chocolate may affect the glycemic response, which is related the insulin and incretin response. We evaluated the glucose, insulin, and glucagon-like peptide-1 (GLP-1) responses in male adults after consumption of three commonly consumed chocolates. Furthermore, we assessed the glycemic index (GI), insulin index (II), and glycemic load (GL) of the chocolates. The study protocol was adapted from the International Standard Organization recommendations. Test foods were chocolate A (milky chocolate), chocolate B (creamy chocolate), chocolate C (chocolate ball), and reference food (glucose solution). Glucose, insulin, and GLP-1 concentrations were assessed at 0, 15, 30, 45, 60, 90, and 120 min after consumption of the test foods. The glycemic responses of the three chocolates were lower than those of the reference food at 30 and 45 min (P

To identify the association between the dietary carbohydrate indexes, such as dietary glycemic index (DGI) and load (DGL), dietary insulin index (DII) and load (DIL), with the possibility of cataract.This case-control study consisted of 101 new cases of cataract and 202 controls. DGI and DGL were computed through DGI values previously published. DII was also calculated based on dietary insulin index data published previously.There was a significant positive association between the highest quartiles of DGI (OR = 6.56; 95% CI = 2.67-16.06; P 0.001), DGL (OR = 6.17; 95% CI = 1.93-19.37; P = 0.002) and DIL (OR = 4.17; 95% CI = 1.41-12.27; P = 0.004) with risk of cataract, compared to those on the lowest quartile, but not for DII (OR = 0.85; 95% CI = 0.39-1.86; P = 0.82). Furthermore, after stratifying groups by BMI, a significant direct association between highest quartile of DGI (OR = 6.76; 95% CI = 2.49-18.38; P 0.001) and DGL (OR = 3.45; 95% CI = 0.96-12.37; P = 0.05) with risk of cataract was evident in individuals with elevated BMI (BMI≥25).We found a significant, direct, relationship between DGI, DGL and DIL with risk of cataract. However, the association between DII and the risk of cataract was not significant, even after adjusting for related confounders.

Background: Despite efforts to control hyperglycemia, diabetes management is still challenging. This may be due to focusing on reducing hyperglycemia and neglecting the importance of hyperinsulinemia; while insulin resistance and resultant hyperinsulinemia preceded diabetes onset and may contribute to disease pathogenesis. Objective: The present narrative review attempts to provide a new insight into the management of diabetes by exploring different aspects of glycemic index and dietary insulin index. Results: The current data available on this topic is limited and heterogeneous. Conventional diet therapy for diabetes management is based on reducing postprandial glycemia through carbohydrate counting, choosing foods with low-glycemic index and low-glycemic load. Since these indicators are only reliant on the carbohydrate content of foods and do not consider the effects of protein and fat on the stimulation of insulin secretion, they cannot provide a comprehensive approach to determine the insulin requirements. Conclusion: Selecting foods based on carbohydrate counting, glycemic index or glycemic load are common guides to control glycemia in diabetic patients, but neglect the insulin response, thus leading to failure in diabetes management. Therefore, paying attention to insulinemic response along with glycemic response seems to be more effective in managing diabetes.

Objective Circulating insulin levels have been positively associated with risk of breast cancer (BrCa); however, it remains unclear whether a diet inducing an elevated insulin response influences Breast risk. Methods In this study, 250 newly diagnosed breast cancer patients and 250 hospitalized controls were recruited using convenience sampling. The dietary insulin index (DII) was calculated by dividing the dietary insulin load by the total energy intake. Results Compared with those in the lowest tertiles of DII and dietary insulin load (DIL), subjects in the highest tertile were more likely to be overweight, have a family history of breast and other types of cancer and a history of benign breast diseases. After controlling for multiple potential confounders, a significantly increased BrCa odds was observed in the highest tertiles of DII and DIL score compared to the lowest tertiles (odds ratio (OR): 1.46; 95% CI: 0.67-3.19, p = 0.006) and (OR: 1.87; 95% CI: 0.92-3.80, p = 0.038), respectively. Conclusions Our findings suggest that a diet that induces an elevated postprandial insulin response, indicated by higher DII and DIL scores, may increase the odds of BrCa, especially among women.

Millets (including sorghum) are known to be highly nutritious besides having a low carbon footprint and the ability to survive in high temperatures with minimal water. Millets are widely recognised as having a low Glycaemic Index (GI) helping to manage diabetes. This systematic review and meta-analyzes across the different types of millets and different forms of processing/cooking collated all evidences. Of the 65 studies that were collected globally, 39 studies with 111 observations were used to analyze GI outcomes and 56 studies were used to analyze fasting, post-prandial glucose level, insulin index and HbA1c outcomes in a meta-analysis. It is evident from the descriptive statistics that the mean GI of millets is 52.7 ± 10.3, which is about 36% lower than in typical staples of milled rice (71.7 ± 14.4) and refined wheat (74.2 ± 14.9). The descriptive, meta and regression analyses revealed that Job's tears, fonio, foxtail, barnyard, and teff were the millets with low mean GI (69). A meta-analysis also showed that all millets had significantly (p < 0.01) lower GI than white rice, refined wheat, standard glucose or white wheat bread except little millet which had inconsistent data. Long term millet consumption lowered fasting and post-prandial blood glucose levels significantly (p < 0.01) by 12 and 15%, respectively, in diabetic subjects. There was a significant reduction in HbA1c level (from 6.65 ± 0.4 to 5.67 ± 0.4%) among pre-diabetic individuals (p < 0.01) who consumed millets for a long period. Minimally processed millets were 30% more effective in lowering GI of a meal compared to milled rice and refined wheat. In conclusion, millets can be beneficial in managing and reducing the risk of developing diabetes and could therefore be used to design appropriate meals for diabetic and pre-diabetic subjects as well as for non-diabetic people for a preventive approach.

The food insulin index (II) is a novel classification to rank foods based on their physiological insulin demand relative to an isoenergetic reference food and may be a valid predictor of postprandial insulin responses and appetite. The present study aimed to compare the postprandial metabolic responses and appetite sensations to two macronutrient- and glycaemic index-matched meals with either high or low II in obese adolescents with insulin resistance (IR). A randomised, single-blind and cross-over trial included fifteen obese adolescents aged 12–18 years with IR. All participants were provided with two different breakfasts: low glycaemic index, low insulin index (LGI-LII) and low glycaemic index, high insulin index (LGI-HII), with a 1-week washout period between meals. At time 0 (just before breakfast), 15, 30, 45, 60, 90, 120, 180 and 240 min after the meal, serum glucose, insulin and C-peptide levels and appetite scores were measured. At the end of 4 h, participants were served ad libitum lunch. Early (0–30 min), late (45–240 min) and total (0–240 min) postprandial insulin responses were lowered by 56·1, 34·6 and 35·6 % after the LGI-LII meal v. LGI-HII meal (P < 0·05). The feeling of hunger was also decreased by 25·8 and 27·5 % after the LGI-LII meal v. LGI-HII meal during the late and total responses (P < 0·05). The calculation II of meals or diets may be a useful dietary approach to reduce postprandial hyperinsulinaemia and the perceived hunger in obese adolescents with IR.

Given the limited research on dietary insulin load (DIL), we examined DIL in relation to cardiovascular risk factors and inflammatory biomarkers in elderly men. For the present cross-sectional study, we recruited 357 elderly men. Dietary intake was assessed using FFQ. DIL was estimated by multiplying the insulin index of each food by its energy content and frequency of consumption and then summing the final value of all food items. After adjustment for covariates, a significant positive association was observed between high DIL with fasting blood sugar (FBS) levels (OR: 7·52; 95 % CI 3·38, 16·75; P=0·0001) and high-sensitive C-reactive protein (hs-CRP) (OR: 3·03; 95 % CI 1·54, 5·94; P=0·001). However, there was no association between high DIL and BMI (OR: 1·43; 95 % CI 0·75, 2·75; P=0·27), serum TAG level (OR: 0·82; 95 % CI 0·26, 2·59; P=0·73), HDL-cholesterol (OR: 2·03; 95 % CI 0·79, 5·23; P=0·13) and fibrinogen (OR: 1·57; 95 % CI 0·80, 3·06; P=0·18). Overall, elderly men with high DIL had higher FBS and hs-CRP levels than those with low DIL. Future studies are needed to clarify the association between DIL and other cardiovascular risk factors in both men and women.

Insulinoma is a pancreatic endocrine tumor lower in size than 20 mm in 80% of the cases and his treatment is chirurgical. However, in certain circumstances such as an occult location or circumstances of metastases, medical treatment is called for. Observation: A 29 years old patient with no specific pathological antecedents has presented severe hypoglycemia mainly in the morning. A patient was in a generally good condition. The fasting test revealed an inappropriate secretion of insulin at a venous glycemia of 0.35 g/l; which was corroborated by Turner index and altered glucose insulin index that we calculated. Moreover, the 8 h cortisolemia was normal at 90.13 ng/l, the TSH was normal at 1.44 μui/l, anti-insulin antibodies were negative at 6.7 U/l; the search of hypoglycemic sulfonamides was negative. Morphologically, she had three pancreatic tomodensitometry these were normal. She also had echo-endoscopy which showed a normal pancreas. The surgical exploration with preoperative echo is advised only after surgeon’s assessment when the technical conditions are not put together. The diagnosis of the occult insulinoma or of nesidioblastosis was retained. The medical treatment was retained. Due to the unavailability of diazoxide in our pharmacies and the high cost of analogs of somatostatine, she was provided with prednisone 0.5 mg/kg/24h which was 40 mg/day after common agreement. The evolution was favorable. Conclusion: It should be noticed that medical treatment can be suggested if insulinoma is not localized. This observation proves that the localization of the insulinoma can be unsuccessful. It should also be noticed that our experience is the fourth described in literature, where hypoglycemia in insulinomas is controlled by prednisone.

Background Data about the relation between dietary insulin load (DIL) and dietary insulin index (DII) with metabolic syndrome (MetS) and obesity are scarce. Therefore, the present study aimed to examine the association of the insulinemic potential of the diet with MetS and obesity amongst Iranian adults. Methods This cross-sectional study was conducted amongst 850 adults aged 20-59 years. Dietary data were collected using a 168-item food frequency questionnaire. DIL was calculated using a standard formula and DII was obtained by dividing DIL by the total energy intake of each participant. The guidelines of the International Diabetes Federation were used to define MetS. General obesity was considered as body mass index ≥ 30 kg/m2 , and abdominal obesity as waist circumference ≥ 94 cm for men and ≥ 80 cm for women. Results Mean DIL and DII values were 101 684 ± 54 802 and 49.4 ± 33.4, respectively. The mean age of participants was 44.9 ± 10.7 years and 36.8%, 28.5% and 48.8% of participants were suffering from MetS, general and abdominal obesity, respectively. In contrast with DIL (P = .73), participants in the last quartile of DII (P = .62) had lower odds of MetS than the first quartile. There were non-significant inverse associations between DIL (P = .91, P = .85) and DII (P = .59, P = .53) with odds of general and abdominal obesity before and after the adjustment of confounders, respectively. Conclusions We did not observe any significant association of DIL and DII with the risk of MetS and obesity amongst the Iranian population. Further prospective studies are needed to confirm the findings of this study.

Background The objectives were to investigate the effect of the interaction between CETP Taq1B polymorphism, Dietary Insulin Index and Insulin Load (DII and DIL) on cardiovascular risk factors among diabetic patients. Methods In this cross-sectional study, blood samples were collected from 220 patients. DIL and DII were obtained via validated FFQ. CETP Taq1B polymorphism was genotyped by the PCR-RFLP method. Results The highest BMI (P = 0.08) and WC (P = 0.01) values were observed in B2B2 genotype with the highest adherence to DII. Patients with B1B1 genotype who were in the highest DIL tertile had lower LDL/HDL (P = 0.001), TG (P = 0.03), and higher HDL (P = 0.02). The highest SOD (P = 0.01), PGF2α (P = 0.04), CRP (P = 0.02), and IL-18 (P = 0.06) was observed in B2B2 genotype carriers with the highest DIL adherence. Individuals with B2B2 genotype in the highest tertile of DII had higher CRP (P = 0.04), TAC (P = 0.01), SOD (P = 0.02), and PGF2α (P = 0.02). B1B1 homozygotes who were in the highest tertile of DII had lower lipid profile TG (P = 0.02), LDL (P = 0.08), and LDL/HDL

Aims Postprandial glycaemic variability carries on being a clinical challenge in optimizing glucose control in type 1 diabetes. The aim of this study was to compare the postprandial glycaemic effects of carbohydrate counting and food insulin index algorithms following the consumption of protein-rich, high-fat meals with different glycaemic index (GI) in adolescents with type 1 diabetes. Methods A randomized, single-blind and crossover trial included 15 adolescents aged 14-18 years with type 1 diabetes. Participants consumed two different test meals with similar energy, macronutrients, and food insulin index but the approximately two-fold difference in GI, in random order on four consecutive mornings at their home. Insulin dose for high- and low-GI test meals were determined by using the carbohydrate counting and food insulin index algorithms. Four-hours postprandial glycaemia was assessed by continuous glucose monitoring system. Results Compared with carbohydrate counting, the food insulin index algorithm significantly decreased peak glucose excursion (-57%, p = 0.02), incremental area under the curve (-65%, p = 0.02) and coefficient variation of blood glucose (-37%, p = 0.03) in the high-GI meal, though there was no difference between two algorithms in the low-GI meal. The occurrence of hypoglycaemia did not significantly differ between insulin dosing algorithms for the high-GI (p = 0.58) and low-GI (p = 0.20) meals. Conclusions The food insulin index algorithm may be beneficial for postprandial glycaemic control after the consumption of high-GI meals in adolescents with type 1 diabetes.

Aims To identify factors predicting a need for insulin therapy in gestational diabetes mellitus (GDM) by comparing plasma glucose (PG) levels in a 75-g oral glucose tolerance test (75-g OGTT) with those in a 500-kcal meal tolerance test (MTT) containing 75 g of carbohydrate. Subjects and methods The MTT was performed in 61 patients who diagnosed with GDM by a 75-g OGTT (age, 33.2 ± 4.5 years; prepregnancy body mass index, 22.6 ± 4.7 kg/m2; number of gestational weeks, 25.1 ± 6.4 weeks). PG and serum insulin levels were measured before the meal and up to 180 min after the meal. The insulin secretion capacity and resistance index were calculated. Results PG levels increased from 86.8 ± 8.8 mg/dL at fasting to 132.7 ± 20.1 mg/dL at 30 min, and 137.8 ± 27.7 mg/dL at 60 min after MTT in the 35 patients with needed insulin therapy; these levels were significantly higher than those in the 26 patients, who only needed diet therapy. The patients with needed insulin therapy had significantly higher fasting PG levels in the 75-g OGTT, PG levels at fasting and 30 min after the MTT, and homeostasis model assessment of insulin resistance (HOMA-IR), and a significantly lower disposition index (DI) and insulin index than patients treated by diet alone. Receiver operating characteristic curve analysis was performed for factors involved in insulin therapy, with the following cutoff values: fasting PG in the 75-g OGTT, 92 mg/dL; PG 30 min after MTT, 129 mg/dL; HOMA-IR, 1.51; DI, 3.9; HbA1c, 5.4%. Multivariate analysis revealed that the 30-min PG level after MTT and HOMA-IR predicted insulin therapy. Conclusion PG levels at 30 min after MTT may be useful for identifying patients with GDM, who need insulin therapy.

Purpose Hyperinsulinemia is related to the development of several chronic diseases, particularly obesity. Therefore, this study aimed to examine the association between the insulinemic potential of both total diet and meals, measured by the glycemic index (GI), glycemic load (GL), insulin index (II), and insulin load (IL), and overweight risk among children and adolescents. Methods This cross-sectional study was conducted on 205 overweight and 146 normal-weight participants aged 6-18 years. Overweight was defined as body mass index >= 85th percentile of Turkish growth-reference data. Through the use of standard methodology, dietary and meal GI, GL, II, and IL were derived from dietary data collected via a 3-day dietary record. Associations were investigated using multivariable-adjusted regression analysis. Results When controlling for potential covariates, a greater dietary II (OR 2.69, 95% CI 1.28, 5.68) and IL (OR 5.22, 95% CI 2.39, 11.38), as well as GL (OR 3.89, 95% CI 1.77, 8.56), was strongly associated with higher odds of overweight (both P-for trend < 0.001). Furthermore, breakfast GL (OR 4.87, 95% CI 2.15, 11.01), II (OR 3.88, 95% CI 1.79, 8.39), IL (OR 4.93, 95% CI 2.20, 11.05) and dinner GL (OR 2.39, 95% CI 1.10, 5.20), II (OR 3.81, 95% CI 1.73, 8.41), IL (OR 3.63, 95% CI 1.67, 7.91) were found to be a significant independent predictor of overweight (all P-for trend < 0.001) in pediatric population. Conclusion Our results suggest that dietary insulin demand, particularly for breakfast and dinner, was independently associated with overweight in children and adolescents. These findings may shed light on the relevance of considering meal insulin demand while developing dietary strategies in this population.

The dietary insulin index directly estimates the postprandial insulin secretion potential of foods, whereas the empirical dietary index for hyperinsulinaemia (EDIH) assesses the insulinaemic potential of usual diets based on fasting plasma C-peptide, and is primarily reflective of insulin resistance. It is unknown whether these insulin-related indices are predictive of an integrated measure of insulin secretion. We conducted a cross-sectional analysis that included 293 non-diabetic men with 24-h urinary C-peptide data from the Men’s Lifestyle Validation Study. EDIH, dietary insulin index and dietary insulin load were calculated using validated FFQ. We conducted multivariable-adjusted linear regression to estimate relative and absolute concentrations of 24-h urinary C-peptide. In multivariable-adjusted models, we found a significant positive association between all three insulin-related dietary indices and 24-h urinary C-peptide (P < 0·05). Relative concentrations of 24-h urinary C-peptide per 1-sd increase in insulin-related dietary indices were 1·12 (95 % CI 1·02, 1·23) for EDIH, 1·18 (95 % CI 1·07, 1·29) for dietary insulin index and 1·16 (95 % CI 1·06, 1·27) for dietary insulin load. When we further adjusted for BMI, the association was attenuated for EDIH, to 1·07 (95 % CI 0·98, 1·16), and remained unchanged for dietary insulin index and dietary insulin load. In conclusion, EDIH, dietary insulin index and dietary insulin load were predictive of integrated insulin secretion assessed by 24-h urinary C-peptide. Findings after adjustment for BMI appear to confirm the relation of EDIH to insulin resistance and dietary insulin index/load to insulin secretion; the respective constructs of the two dietary indices.

Background The present study was conducted to investigate the association of dietary insulin index(II), insulin load(IL), glycemic index(GI), and glycemic load(GL) with the risk of cardiovascular disease(CVD). Methods This cohort study was conducted within the framework of the Tehran Lipid and Glucose Study on 2198 subjects, aged≥19 years old, who were followed-up for a median (IQR) 6.7 (6.1–7.1) years. Dietary GI, GL, II, and IL were calculated using a food frequency questionnaire at the baseline. Multivariate Cox proportional hazard regression models were used to estimate the risk of CVD across quartiles of dietary insulin and glycemic indices. Results Mean ± SD age of the subjects(44.9% men) was 38.3 ± 13.4 years. During a mean of 2406 ± 417 person-years of follow-up, 76(3.5%) new cases of the CVD were ascertained. The mean ± SD of II, IL, GI, and GL of participants were 51.7 ± 6.5, 235.8 ± 90.2, 61.9 ± 7.8, and 202.2 ± 78.1, respectively. After adjusting for the variables of age, sex, smoking, physical activity, daily energy intake, body mass index, diabetes, and hypertension, the hazard ratio (HR) of the highest quartile of dietary GL was 2.77(95%CI:1.00–7.69,P for trend:0.033) compared to the lowest one. Also, each one SD increase in the GL score was associated with a higher risk of CVD[(RR:1.46;CI:1.00–2.16),P-value = 0.047]. However, there was no significant association between the dietary GI, II, and IL and risk for CVD incidence. Conclusions Our results suggested that a high GL diet can increase the incidence of CVD, whereas high dietary II and IL were not associated with the risk of CVD among adults.

Summary Background and aim The aim of this study was to investigate the association of dietary insulin index(II), insulin load(IL), glycemic index(GI), and glycemic load(GL) with risk of developing diabetes among the Tehranian adults. Methods This study was conducted within the framework of the Tehran Lipid and Glucose Study on 1149 subjects, aged ≥30 years, who were followed-up for a mean of 8.04 years. Food frequency questionnaire was used to calculate the dietary GI, GL, II, IL at the baseline. Multivariate Cox proportional hazard regression models, adjusted for the potential confounders, were used to estimate the risk of diabetes based on the dietary indices. Results Mean age of the study population was 44.8 ± 10.4 years and 46.3% of them were men. During a mean of 8.04 ± 2.1 years of follow-up, 76 (6.6%) new cases of diabetes were identified. The mean ± SD of the II, IL, GI, and GL of the participants were 52.4 ± 6.5, 234.9 ± 88.8, 61.8 ± 7.9, and 200.6 ± 74.5, respectively. After adjusting for age, sex, smoking, physical activity, daily energy intake, and body mass index, higher dietary scores of the II[HR = 1.33 (95%CIs = 1.06–1.68)], IL[HR = 1.70(95%CIs = 1.10–2.60)], GI[HR = 1.28(95%CIs = 1.03–1.60)], and GL[HR = 1.84 (95%CIs = 1.19–2.84)] were found to be associated with the increased risk of diabetes incidence per each ones SD increment in the scores. Considering the tertiles of the dietary scores, the risk of developing diabetes was increased significantly from tertile 1 into 3 of the GL, and after adjusting for all the potential covariates (p-trend = 0.002); the diabetes risk was 3.40 (95%CI:1.48–7.83) in those with highest tertile of GL compared to those in the lowest tertile of GL. Conclusion Our findings suggest that the diet with high GL, GI, II, and IL can increase the incidence of diabetes. The glycemic and insulin load can strongly predict the risk of diabetes rather than the glycemic index and insulin index.

Vacuolar H+-adenosine triphosphatase (V-ATPase) stimulates vesicular acidification that may activate cytoplasmic enzymes, hormone secretion and membrane recycling of transporters. We investigated the effect of blockade of V-ATPase by bafilomycin B1 on renal gluconeogenesis, mitochondrial enzymes, and insulin secretion in type 2 diabetic rats. Spontaneous type 2 diabetic Torii rats were treated with intraperitoneal injection of bafilomycin B1 for 1 week, and the kidneys were examined after 24 h of starvation in metabolic cages. The renal expression and activity of V-ATPase were increased in the brush border membrane of the proximal tubules in diabetic rats. The blockade of V-ATPase by bafilomycin B1 reduced renal V-ATPase activity and urinary ammonium in diabetic rats. Treatment with bafilomycin suppressed the enhanced renal gluconeogenesis enzymes and mitochondrial electron transport enzymes in type 2 diabetic rats and reduced the renal cytoplasmic glucose levels. The insulin index and pancreatic insulin granules were decreased in diabetic rats with increased V-ATPase expression in islet cells, and treatment with bafilomycin B1 reversed these changes and increased the insulin secretion index. Hepatosteatosis in type 2 diabetic rats was ameliorated by bafilomycin treatment. As a consequence, treatment with bafilomycin B1 significantly decreased the plasma glucose level after 24 h of starvation in diabetic rats. In conclusion, a V-ATPase inhibitor improved plasma glucose levels in type 2 diabetes by inhibiting renal mitochondrial gluconeogenesis and improving insulin secretion.

Ethnopharmacological relevance Corn silk is composed of the style and stigma of Zea mays L. Its medical value was first reported in “Southern Yunnan Materia Medica” in the Ming Dynasty. It was considered to be a heat-clearing and diuretic drug. In “Zhejiang Folk Herbal Medicine,” the following has been reported: “Corn silk needs one liang. Decoction in water can cure diabetes.” Recent studies have shown that corn silk can lower blood sugar levels; however, to date, corn silk has undergone simple pharmacodynamic evaluations, with both its degree and mechanism of action remaining unclear. Aim of the study This study aimed to investigate the mechanism of action of corn silk, with respect to having antioxidative ability, reducing insulin resistance, and having a hypoglycemic effect. Materials and methods In this study, a type 2 diabetes mellitus (T2DM) rat model was established via a high sugar and high fat diet combined with streptozotocin (35 mg/kg) administration. Wistar rats were administered corn silk decoction and metformin via gavage for four weeks, and the fasting blood glucose (FBG) and body weight were measured every two weeks. After the experiment, the insulin level, insulin index, and glycogen content were determined. Hematoxylin-eosin staining was used to observe the morphological changes of the skeletal muscle tissue in rats. The levels of malondialdehyde and superoxide dismutase in the serum and skeletal muscle were detected, and the mRNA content and protein levels of key proteins in the JNK-IRS-GLUT4 signaling pathway were determined using real-time quantitative polymerase chain reaction and western blotting. Then, ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry, combined with multiple statistical analyses, was used to identify potential biomarkers in the serum of T2DM rats, for determining the key metabolic pathways responsible for the action of corn silk. Results The results showed that corn silk could reduce FBG, insulin level, and glycogen content in T2DM rats; reduce the level of oxidative stress in serum and skeletal muscle; restore the pathological structure of skeletal muscle; inhibit the phosphorylation of c-Jun N-terminal kinase (JNK) and insulin receptor substrate (IRS) in skeletal muscle; and upregulate the expression of glucose transporter type 4 (GLUT4) for transport of glucose and to reduce insulin resistance. Moreover, metabonomic analysis elucidated that corn silk could significantly affect 26 biomarkers (such as pentosidine, palmitic acid, lysoPC, and p-Cresol sulfate) and metabolic pathways (such as phenylalanine metabolism, phospholipid metabolism, bile acid metabolism, and biosynthesis of unsaturated fatty acids). Conclusion The interaction between endogenous metabolites and proteins in signaling pathways was analyzed using metabonomics and molecular biology methods. Corn silk inhibited JNK-IRS-GLUT4 signal transduction in skeletal muscle via antioxidative effects, by increasing the sensitivity of peripheral tissue to insulin, by reducing insulin resistance, and through hypoglycemic effects.