Insulin resistance—the silent epidemic we learn about too late?

Aim of the study: The effect of diet on insulin resistance (IR) in polycystic ovary syndrome (PCOS) is controversial. Thus, we conducted this systematic review and meta-analysis to evaluate whether diet could reduce IR in women with PCOS while providing optimal and precise nutrition advice for clinical practice.

Results: A total of 19 trials (1193 participants) were included. The analysis showed that diet was significantly related to improvements in IR and body composition (eg, homeostasis model assessment of insulin resistance, fasting insulin, fasting plasma glucose, body mass index [BMI], weight, and waist circumference) in PCOS patients. The Dietary Approaches to Stop Hypertension diet and calorie-restricted diets might be the optimal choices for reducing IR and improving body composition, respectively, in the PCOS population. Additionally, the effects were associated with the course of treatment. The longer the duration, the greater the improvement was. Compared with metformin, diet was also advantageous for weight loss (including BMI and weight) and had the same effects on insulin regulation. Overall, our findings suggest that diet is an effective, acceptable and safe intervention for relieving IR, and professional dietary advice should be offered to all PCOS patients.

Aim of the study: The optimal dietary pattern to improve metabolic function remains elusive. In a 21-day randomized controlled inpatient crossover feeding trial of 20 insulin-resistant obese women, we assessed the extent to which two isocaloric dietary interventions-Mediterranean (M) and high protein (HP)-improved metabolic parameters.

Results: Compared to the M diet, the HP diet was more effective in (i) reducing insulin resistance (insulin: Beta (95% CI) = -6.98 (-12.30, -1.65) µIU/mL, p = 0.01; HOMA-IR: -1.78 (95% CI: -3.03, -0.52), p = 9 × 10-3); and (ii) improving glycemic variability (-3.13 (-4.60, -1.67) mg/dL, p = 4 × 10-4), a risk factor for T2D development. We then identified a panel of 10 microbial genera predictive of the difference in glycemic variability between the two diets. These include the genera Coprococcus and Lachnoclostridium, previously associated with glucose homeostasis and insulin resistance. Our results suggest that morbidly obese women with insulin resistance can achieve better control of insulin resistance and glycemic variability on a high HP diet compared to an M diet.

Aim of the study: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders among reproductive-aged women. It is characterized by hyperandrogenism, anovulation, and polycystic ovaries.

Results: Dietary interventions such as foods with low glycemic index scores; caloric restrictions; high-fiber, omega three fatty acid-rich diets; ketogenic diets; Mediterranean diets; antioxidant-rich food; and anti-inflammatory diets improve insulin sensitivity and hormonal balance in women with PCOS. Physical activity, like aerobic and resistance exercise, enhances insulin sensitivity, helps weight loss, and improves metabolic and reproductive outcomes in women with PCOS. Further, behavioral and education modules can also be used to improve awareness, adherence, and the effectiveness of conventional treatment and to manage mental health issues related to PCOS. Collectively, lifestyle modifications not only improve the biochemical, hormonal, and anthropometric parameters in PCOS patients but also reduce the long-term risks of metabolic and cardiovascular diseases.

Aim of the study: Insulin resistance (IR) is a hallmark of metabolic disorders including type 2 diabetes mellitus (T2DM), metabolic syndrome, metabolic dysfunction-associated steatotic liver disease (MASLD), obesity, polycystic ovary syndrome (PCOS), and cardiovascular diseases. It arises from impaired insulin signaling in muscle, liver, and adipose tissue, driven by ectopic lipid accumulation, chronic inflammation, oxidative stress, and gut microbiota dysbiosis.

Results: IR assessment relies on the hyperinsulinemic-euglycemic clamp as gold standard, with HOMA-IR and QUICKI as validated clinical surrogates. The Mediterranean diet is the most evidence-supported strategy, with consistent HOMA-IR reductions, a 31% decrease in T2DM incidence (PREDIMED-Plus), and demonstrated efficacy across T2DM, MASLD, and PCOS. Low-GI and DASH diets improve postprandial insulin dynamics and are particularly effective in PCOS. Low-carbohydrate and ketogenic diets produce the largest short-term reductions in fasting glucose and insulin secretion, though long-term sustainability requires further study. Plant-based diets and intermittent fasting improve IR primarily via weight loss and gut microbiota modulation. Most studies rely on surrogate IR indices and are short-term (≤26 weeks). Dietary pattern selection should be individualized according to metabolic phenotype, comorbidities, and adherence potential.

Aim of the study: As years progress, we are found more often in a postprandial than a postabsorptive state. Chrononutrition is an integral part of metabolism, pancreatic function, and hormone secretion.

Results: Lifestyle interventions with small weight loss (7-10%), 150 min of weekly moderate intensity exercise and behavioral therapy approach can be highly effective in preventing and treating type 2 diabetes. Similarly, decreasing carbohydrates in meals also improves significantly glycemic and insulin responses, but the extent of this reduction should be individualized, patient-centered, and monitored. Alternative foods or ingredients, such as vinegar, yogurt, whey protein, peanuts and tree nuts should also be considered in ameliorating postprandial hyperglycemia and insulin resistance. This review aims to describe the available evidence about the effects of diet, chrononutrition, alternative dietary interventions and exercise on postprandial glycemia and insulin resistance.

Aim of the study: Over the past 30 years, a significant increase in the prevalence of insulin resistance (IR) has been observed. It is associated with more frequent occurrence of impaired glucose tolerance, diabetes, excessive weight, cardiovascular diseases, and endocrine disorders.

Results: The beneficial effect of the Dietary Approaches to Stop Hypertension (DASH diet) and the Mediterranean diet has been confirmed. The positive correlation between low-carbohydrate and very-low-carbohydrate diets requires confirmation in long-term studies with the participation of insulin-resistant patients. Research shows the benefits of increased calorific intake during the first half of the day, especially from a high-energy and low-glycemic-index breakfast. Furthermore, many researchers indicate that slow and mindful eating is a significant component of an appropriate diet for insulin-resistant individuals.

Aim of the study: Precision nutrition based on metabolic phenotype may increase the effectiveness of interventions. In this proof-of-concept study, we investigated the effect of modulating dietary macronutrient composition according to muscle insulin-resistant (MIR) or liver insulin-resistant (LIR) phenotypes on cardiometabolic health.

Results: Women and men with MIR or LIR (n = 242, body mass index [BMI] 25-40 kg/m2, 40-75 years) were randomized to phenotype diet (PhenoDiet) group A or B and followed a 12-week high-monounsaturated fatty acid (HMUFA) diet or low-fat, high-protein, and high-fiber diet (LFHP) (PhenoDiet group A, MIR/HMUFA and LIR/LFHP; PhenoDiet group B, MIR/LFHP and LIR/HMUFA). PhenoDiet group B showed no significant improvements in the primary outcome disposition index, but greater improvements in insulin sensitivity, glucose homeostasis, serum triacylglycerol, and C-reactive protein compared with PhenoDiet group A were observed. We demonstrate that modulating macronutrient composition within the dietary guidelines based on tissue-specific insulin resistance (IR) phenotype enhances cardiometabolic health improvements. Clinicaltrials.gov registration: NCT03708419, CCMO registration NL63768.068.17.

Aim of the study: Insulin resistance (IR), defined as an attenuated biological response to circulating insulin, is a fundamental defect in obesity and type 2 diabetes (T2D), and is also linked to a wide spectrum of pathological conditions, such as non-alcoholic fatty liver disease (NAFLD), cognitive impairment, endothelial dysfunction, chronic kidney disease (CKD), polycystic ovary syndrome (PCOS), and some endocrine tumors, including breast cancer.

Results: In obesity, the unbalanced production of pro- and anti-inflammatory adipocytokines can lead to the development of IR and its related metabolic complications, which are potentially reversible through weight-loss programs. The Mediterranean diet (MedDiet), characterized by high consumption of extra-virgin olive oil (EVOO), nuts, red wine, vegetables and other polyphenol-rich elements, has proved to be associated with greater improvement of IR in obese individuals, when compared to other nutritional interventions. Also, recent studies in either experimental animal models or in humans, have shown encouraging results for insulin-sensitizing nutritional supplements derived from MedDiet food sources in the modulation of pathognomonic traits of certain IR-related conditions, including polyunsaturated fatty acids from olive oil and seeds, anthocyanins from purple vegetables and fruits, resveratrol from grapes, and the EVOO-derived, oleacein.

Aim of the study: The aim of this study was to explore the effects of a low-fat plant-based diet on hepatocellular and intramyocellular lipids, advanced glycation end products (AGEs), insulin resistance, and beta-cell function in adults with type 2 diabetes.

Results: Mean body weight decreased by 6.0 kg (95% CI -7.0 to -5.1; p<0.001), a 6.6% (95% CI -7.5 to -5.8) decrease relative to baseline. This was largely due to the reduction in fat mass (-4.2 kg, 95% CI -5.7 to -2.7; p<0.001). Visceral fat volume decreased by 290 cm3 (95% CI -467 to -114; p=0.003). Hepatocellular lipids decreased by 33.0% (95% CI -48.7 to -17.3; p<0.001). The AGE score decreased by 0.4 (95% CI -0.6 to -0.2; p=0.002). The HOMA-IR index, a measure of insulin resistance, fell (-2.5, 95% CI -4.1 to -0.9; p=0.004), whereas PREDIM, a measure of insulin sensitivity, increased on the vegan diet (+1.3 mg/min/kg, 95% CI +0.6 to +2.1; p=0.002). Several markers of beta-cell function improved on the vegan diet. Specifically, insulin secretion at 6 and 7 mmol/L glucose, beta-cell glucose sensitivity, rate sensitivity, and potentiation factor all increased.

Aim of the study: Obesity disrupts glucose homeostasis and insulin signaling, partly through altered gut hormone secretion and intestinal inflammation. Our previous work demonstrated that fructooligosaccharides (FOS), a prebiotic fiber, suppressed colonic inflammation, and modulated gut microbiota when administered with vitamin D supplementation.

Results: FOS attenuated HFD-induced metabolic dysfunction, lowering serum insulin and HOMA-IR in both sexes. Notably, FOS elicited sex-dependent physical improvements of which it suppressed body weight gain by 10% in male mice and reduced visceral fat accumulation by 36% in female mice. The phenotypic changes in male mice were associated with an increase in GLP-1. Further, FOS modulated colonic PI3K/Akt signaling in a sex-dependent manner and downregulated HFD-associated increases in Glp1r mRNA expression. Consistent with our previous work, FOS suppressed RI abundance, and this reduction was associated with lower colonic Tlr4 mRNA expression and improved insulin-resistance index. FOS improves insulin sensitivity in HFD-induced obesity and specifically enhanced GLP-1 production in male mice. Though the mechanism remained elucidated, the observed phenotype changes may be attributed to a combination of altered colonic PI3K/Akt pathways and targeted bacterial shifts.