Table 2.
A summary of the clinical trials reporting on the non-pharmacological interventions used in the management of insulin resistance (IR).
| Trial | Design | Intervention | Results |
|---|---|---|---|
| Kahleova et al.170 | 24-week, randomized, open, parallel, metabolically controlled design enrolling 74 subjects with T2D | Isocaloric, calorie-restricted vegetarian or conventional diabetic diet for the first 12 weeksplusAerobic exercise in the second 12 weeks | Insulin sensitivity improved significantly with vegetarian meals, compared with the control group (30% [95% CI 24.5, 39] versus 20% [95% CI 14, 25], P = 0.04).Body weight decreased more in the experimental group than in the control group (–6.2 kg [95% CI –6.6, –5.3] versus –3.2 kg [95% CI –3.7, –2.5]; interaction group X time P = 0.001). Reduction in visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Alterations in insulin sensitivity and oxidative stress markers correlated with visceral fat loss. Adiponectin increased (P = 0.02) and leptin decreased (P = 0.02). Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Greater changes when exercise was added. |
| PREDIMED study172 | Multicentered, randomized, nutritional interventional trial involving 7447 subjects free of CVD at baseline but with high risk for CVD from 2003 to 2011 | MedDiet plus extra virgin olive oil (EVOO) orMedDiet plus nutsorControl diet, low in fat content | 288 CVD events during a median follow-up time of 4.8 years; hazard ratios: 0.69 (95% CI 0.53, 0.91) for the MedDiet plus EVOO and 0.72 (CI 0.54, 0.95) for the MedDiet plus nuts compared with the control group. 30% risk reduction in the incidence of major cardiovascular events with a per-protocol (adherence-adjusted) reduction of 58%. |
| Velazquez-Lopez et al.173 | Open-label, randomized controlled interventional trial on 49 children from another study related to the management of T2D in pediatric patients | MedDiet or standard diet for 16 weeks | 10.5% decrement (95% CI –13.1, –7.7) in glucose levels compared with a 4.9% decrease (95% CI –8.1, –1.7) in the standard diet. Decrease in glucose levels and frequency of glucose >100 mg/dl (P < 0.05). 45% decrease in metabolic syndrome, BMI, lean and fat mass. |
| Tettamanzi et al.174 | 21-day randomized controlled inpatient crossover feeding trial in 20 IR women, 16 of whom completed the trial | MedDiet versus high protein (HP) diet | HP diet: more effective in: (i) reducing insulin resistance (insulin: Beta = −6.98 (95% CI –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 (95% CI –4.60, –1.67) mg/dl, P = 4 × 10−4), a risk factor for T2D development. Favorable alteration in gut microbiota composition |
| Shang et al.176 | Systematic review of 19 trials with 1193 participants with PCOS | Dietary interventions | 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 women with PCOS. |
| Sutton et al.178 | 5-week, proof-of-concept, isocaloric and eucaloric randomized controlled feeding trial in prediabetic men | Early-time restricted feeding (eTRF) versus control | eTRF decreased fasting insulin by 3.4 ± 1.6 mU/l (P = 0.05) and decreased insulin levels at t = 60 min and 90 min post-load (P ≤ 0.01) eTRF increased the insulinogenic index (b cell responsiveness) by 14 ± 7 U/mg (P = 0.05) and decreased insulin resistance (3-h incremental AUC ratio) by 36 ± 10 U/mg (P = 0.005). Decreased morning levels of systolic and diastolic blood pressure by 11 ± 4 mmHg (P = 0.03) and 10 ± 4 mmHg (P = 0.03), respectively, compared with the control schedule. No effects on arterial stiffness (unaltered augmentation index [Δ = −1.4% ± 2.1%; P = 0.53] or pulse wave velocity [Δ = −0.5 ± 0.4 m/s; P = 0.23]), HDL-C (Δ = −0.6 ± 0.9 mg/dl; P = 0.48) or LDL-C (Δ = 2 ± 6 mg/dl; P = 0.75). Decreased plasma levels of 8-isoprostane, a marker of oxidative stress to lipids, by 11 ± 5 pg/ml (P = 0.05) or approximately 14%.No effects on hs-CRP (Δ = −0.3 ± 1.0 mg/l; P = 0.77), cortisol (Δ = −0.1 ± 1.3 mg/dl; P = 0.95) or IL-6 (Δ = 0.45 ± 0.27 pg/ml; P = 0.12). No effects on appetite. |
| Harvie et al.179 | 6-month randomized controlled interventional trial in 107 premenopausal young overweight women | IER versus CER | Greater impact of IER in IR reduction and fasting insulin levels: the difference between the groups for fasting insulin was –1.2 μU/ml (95% CI –1.4, –1.0 µU/ml); and for insulin resistance it was –1.2 μU/mmol/l (95% CI –1.5, –1.0) (both comparisons P = 0.04). Both IER and CER were equally effective in weight loss (–6.4 kg [95% CI –7.9, –4.8 kg] for IER versus –5.6 kg [95% CI –6.9, –4.4 kg] for CER). Percentage of fat loss in the IER and CER groups was 79% (±24%) and 79% (±26%), respectively (P = 0.99). Modest increase in adiponectin in the IER group, but not in the CER group (mean difference [95% CI] +9 [–2, 21%], P = 0.08). Modest decreases in the inflammatory marker hs-CRP. Oxidation protein products appeared to decrease in the IER group and to have a slight increase in the CER group (mean difference between groups at 6 months [95% CI]: –10 [–19, 2%], P = 0.12). |
| Villarreal-Calderón et al.184 | Systematic review assessing 19 543 patients | Metabolic surgery | CVD factors were improved. 73% of subjects presented resolution or remission of T2D. |
| Katzmarzyk et al.187 | Observational cohort study with clinical evaluation of 19 223 men from 1979 to 1995 with mortality follow-up through to December 1996 | Cardiorespiratory fitness (CRF) inclusion | No CRF: RR for all-cause and CVD mortality was 1.29 and 1.89, respectively, for men with metabolic syndrome compared with healthy men. CRF: RR 0.98 for all-cause and 1.23 for CVD mortality, when metabolic syndrome was present. |
| Katzmarzyk et al.188 | Observational cohort study including 19 173 men | CRF inclusion | Risks of all-cause mortality were 1.11 (0.75, 1.17) in normal weight, 1.09 (0.82, 1.47) in overweight and 1.55 (1.14, 2.11) in obese men with MetS compared with normal weight healthy men. Risks for CVD mortality were 2.06 (0.92, 4.63) in normal weight, 1.80 (1.10, 2.97) in overweight and 2.83 (1.70, 4.72) in obese men with the MetS compared with normal weight healthy men. After the inclusion of CRF in the model, the risks associated with obesity and metabolic syndrome were no longer significant. |
| Laaksonen et al.189 | Prospective population-based cohort study of 612 middle-aged men, 4-year follow-up | Leisure-time physical activity (LTPA) | Men engaging in 3 h/week of moderate or vigorous LTPA were half as likely as sedentary men to have the MetS after adjustment for major confounders or potentially mediating factors. Men in the upper third of VO2max were 75% less likely than unfit men to develop the MetS, even after adjustment for major confounders. Vigorous LTPA had an even stronger inverse association, particularly in unfit men. |
| Sampath Kumar et al.190 | Meta-analysis involving 846 diabetic patients | Structured exercise programs | The standardized mean difference in the intervention group for fasting insulin levels, HOMA-IR, fasting blood sugar, HbA1c and BMI was: –1.64, 0.14, –5.12, 0.63 and –0.36, respectively, compared with the control group. |
| Motahari-Tabari et al.191 | Randomized controlled clinical trial enrolling 53 diabetic women for 8 weeks | Aerobic exercise protocol versus control | Intervention group: lower plasma glucose (P = 0.05), insulin levels (P = 0.000) and insulin resistance (P = 0.02) compared with the control group. |
| Nery et al.193 | Meta-analysis of eight articles with 336 subjects in total | Protocols of aerobic and resistance exercise, varying in duration and frequency | Resistance training in diabetic adults was found to be more effective at increasing maximal oxygen consumption (mean difference: –2.86; 95% CI –3.90, –1.81; random effect) within 12 weeks or longer, with no apparent differences concerning HbA1c, BMI and lipid profile when compared with aerobic training. |
| Fedewa et al.194 | Meta-analysis of 24 studies | Exercise training on fasting insulin | A small-to-moderate effect was found for exercise training on fasting insulin and improving insulin resistance in youth (Hedges’ d effect size = 0.48 [95% CI 0.22, 0.74], P < 0.001 and 0.31 [95% CI 0.06, 0.56], P < 0.05, respectively). |
| Marson et al.195 | Meta-analysis of 17 studies | Exercise training in general and evaluation of aerobic, resistance exercise or their combination | Physical exercise improved fasting insulin levels and HOMA-IR (fasting insulin: –3.37 μU/ml; 95% CI –5.16, –1.57 μU/ml; I2 54%, P = 0.003); HOMA-IR: –0.61; 95% CI –1.19, –0.02; I2 49%, P = 0.040), but not fasting glucose levels. Evaluation of aerobic, resistance training or their combination showed that aerobic exercise is clearly more efficient in reducing insulin levels and HOMA-IR (fasting insulin: –4.52 μU/ml; 95% CI –7.40, –1.65; I2 65%, P = 0.002); HOMA-IR: –1.33; 95% CI –2.47, –0.18; I2 73%, P = 0.005). |
T2D, type 2 diabetes mellitus; CI, confidence interval; CVD, cardiovascular disease; MedDiet, Mediterranean diet; BMI, body mass index; HOMA-IR, homeostasis model assessment-insulin resistance; PCOS, polycystic ovary syndrome; AUC, area under the curve; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; hs-CRP, high-sensitivity C-reactive protein; IL-6, interleukin-6; IER, intermittent energy restriction; CER, continuous energy restriction; RR, relative risk; MetS, metabolic syndrome; HbA1c, glycosylated hemoglobin.