Potential Role of Nut Consumption for Improving Insulin Sensitivity : Results from a Systematic Review and Meta-analysis of Randomized Controlled Trials

Potential Role of Nut Consumption for Improving Insulin Sensitivity : Results from a Systematic Review and Meta-analysis of Randomized Controlled Trials

By Heather Nelson Cortes, PhD and Kevin C Maki, PhD


Worldwide incidence and prevalence of type 2 diabetes mellitus (T2D) diabetes are increasing at alarming rates, largely following increases in incidence of overweight and obesity.  The World Health Organization reports that ~1.9 billion adults are overweight in 2019, including 600 million that are obese and thus at heightened risk for T2D1.  Overweight and obesity are associated with impaired whole-body insulin sensitivity (i.e., increased insulin resistance), which is believed to be the key pathophysiologic link to increased risk for T2D 2.


Many epidemiological studies have examined the association of nut consumption with risks for T2D and mortality.  Systematic reviews and meta-analyses of prospective cohort studies have suggested a reduction in T2D risk with regular nut consumption 3-5


Tindall and colleagues recently published a review of 40 randomized, controlled trials with a median duration of 3 months (N = 2,832 subjects), that examined the effects of consuming tree nuts and peanuts on glycemic markers, including homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin and glucose, and glycated hemoglobin (HbA1C) 6.  The median intake of nuts was 52 g/d (range: 20-113 g/d).


In pooled analyses, consumption of tree nuts or peanuts reduced both HOMA-IR (weighted mean difference [WMD] −0.23; 95% confidence interval [CI] −0.40, −0.06; I2 = 51.7%) and fasting insulin (WMD −0.40 μU/mL; 95% CI −0.73, −0.07 μU/mL; I2 = 49.4%) compared to the control conditions 6.  However, there were no effects of nut consumption on fasting blood glucose (WMD −0.52 mg/dL; 95% CI −1.43, 0.38 mg/dL; I2 = 53.4%) or HbA1C (WMD 0.02%; 95% CI −0.01%, 0.04%; I2 = 51.0%).
 Further analyses showed no associations between the dose of nuts/peanuts consumed and the mean difference between nut and control treatments for any of the measured outcomes.  Analysis by nut type showed no deviations from the main results.


Comment. While there were no effects of nut consumption on HbA1C or fasting glucose, there were statistically significant reductions in HOMA-IR and fasting insulin, suggesting improved insulin sensitivity.  Future studies are needed to help determine the mechanisms through which nut/peanut consumption affects insulin sensitivity. 



  1. World Health Organization. Global report on diabetes. Geneva, Switzerland: World Health Organization; 2016. 

  2. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444:840–6.
  3. Afshin A, Micha R, Khatibzadeh S, Mozaffarian D. Consumption of nuts and legumes and risk of incident ischemic heart disease, stroke, and diabetes: a systematic review and meta-analysis. Am J Clin Nutr 2014;100(1):278–88. 

  4. Aune D, Keum N, Giovannucci E, et al. Nut consumption and risk of cardiovascular disease, total cancer, all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis of prospective studies. BMC Medicine 2016;14(1):207.
  5. Luo C, Zhang Y, Ding Y, et al. Nut consumption and risk of type 2 diabetes, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis. Am J Clin Nutr 2014;100(1):256–69. 

  6. Tindall AM, Johnston EA, Kris-Etherton PM, Petersen KS. The effect of nuts on markers of glycemic control: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2019;109:297–314.


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Viscous Fiber Supplements in Diabetes Control: Results from a Systematic Review and Meta-analysis of Randomized Controlled Trials

Viscous Fiber Supplements in Diabetes Control: Results from a Systematic Review and Meta-analysis of Randomized Controlled Trials

By Heather Nelson Cortes, PhD and Kevin C Maki, PhD

According to the recent 2019 American Diabetes Association (ADA) Standards of Medical Care in Diabetes, people with diabetes should increase their intake of viscous fiber from sources such as oats, legumes, and citrus to help regulate blood glucose levels and lower risk of cardiovascular disease1. Viscous fibers are described as such because they increase viscosity in the human gut, thereby reducing the rate at which carbohydrates are digested and the glucose molecules from them absorbed.  These effects occur because the viscous solution impedes the ability of digestive enzymes to reach starch molecules and slows the rate at which glucose molecules reach the brush border in the intestinal lumen, where absorption can occur.  The result is flattening of the postprandial glycemic and insulinemic responses.  While these acute effects are well established, the longer-term impacts of viscous fibers on glycemic control markers are not well known2.


In a systematic review and meta-analysis, Jovanovski2 investigated the effect of viscous dietary fiber supplementation on markers of glycemic control in people with type 2 diabetes (T2D).  A comprehensive literature search on MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through June 15, 2018 identified 2,716 potential RCTs.  After reviewing the studies based on the inclusion/exclusion criteria, 27 studies (n = 1,394) were identified for the review and meta-analysis.  Inclusion criteria were: ≥3 weeks in duration, studied viscous fiber supplementation (β-glucan, guar gum, konjac, psyllium, pectin, xanthan gum, locust bean gum, alginate, agar) compared to an appropriate control (i.e., fiber-free supplement or one containing insoluble fiber, background diet, or placebo), and included at least one glycemic measurement (glycated hemoglobin [HbA1c], fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance [HOMA-IR], or fructosamine).


The median age of subjects was 60 years (range 48-67) and they had a median body mass index of 27 kg/m2 (range 26-32 kg/m2).  The median dose of viscous fibers in the studies was 13.1 g/day (range 2.55-21.0 g/day) and the median study duration was 8 weeks (range 3-52 weeks).


Compared to control groups, inclusion of viscous fiber in the diet was associated with significant reductions in HbA1c, fasting blood glucose and HOMA- IR. 


  • HbA1c: mean difference (MD) -0.58% 95% confidence interval (CI) -0.88%, -0.28%; p = 0.0002;
  • Fasting blood glucose: MD -14.8 mg/dL 95% CI -23.8, -5.59; p = 0.001
  • HOMA-IR: MD -1.89 95% CI -3.45, -0.33; p = 0.02.


There were no differences between viscous fiber groups and controls for fasting insulin (MD -2.53 µU/mL 95% CI -5.41, 0.35; p = 0.08) or fructosamine (MD -0.12 mmol/L 95% CI -0.39, 0.14; p = 0.37).  Only 2 studies reported fructosamine, so this finding should be interpreted with caution.  There was no evidence of a significant dose-response effect.  Results for HbA1c, fasting glucose, fasting insulin, and HOMA-IR were graded moderate for certainty of evidence, while fructosamine was graded low.


Comment.  Viscous fiber intake, through consumption of food sources such as legumes, whole fruits (e.g., apples and pears) and whole grain oats and barley, as well as dietary supplementation with products such as psyllium (e.g., Metamucil®), methylcellulose (e.g., Citrucel®) or konjac (e.g., Lipozene®), appears to have several benefits regarding cardiometabolic health.  For those with T2D, this meta-analysis shows evidence to support favorable effects on glycemic control and insulin sensitivity.  More research is needed to establish more clearly whether all viscous fibers enhance insulin sensitivity, or whether this property is limited to those with certain characteristics, such colonic fermentability or content of specific bioactive compounds3,4.  Evidence from other sources also shows that viscous fiber lowers the circulating cholesterol level, likely by trapping cholesterol and bile acids, thus preventing their absorption/reabsorption3.  In addition, viscous fibers appear to play a role in appetite regulation, enhancing satiety after meal5.


The meta-analysis by Jovanovski and colleagues shows that inclusion of viscous fiber in the diet produces clinically meaningful improvements in glycemic control for patients with T2D.  Based on this, as well as evidence for other benefits (cholesterol lowering and enhanced satiety), inclusion of viscous fiber from foods and/or supplements should be considered an important component of the management plan for patients with T2D.



  1. American Diabetes Association. 10. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2019. Diabetes Care. 2019;42(Supplement 1): S103-S123.


  1. Jovanovski E, Khayyat R,  Zurbau A,  et al. Should viscous fiber supplements be considered in diabetes control? Results from a systematic review and meta-analysis of randomized controlled trials. Diabetes Care. 2019 Jan; doi:10.2337 [Epub ahead of print].


  1. Weickert MO, Pfeiffer AFH. Impact of dietary fiber consumption on insulin resistance and the prevention of type 2 diabetes. J Nutr. 2018;148:7-12.


  1. Kärkkäninen O, Lankinen MA, Vitale M, et al. Diets rich in whole grains increase betainized compounds associated with glucose metabolism. Am J Clin Nutr. 2018;108:971-979.


  1. Rebello CJ, Chu YF, Johnson WD, et al. The role of meal viscosity and oat ß–glucan characteristics in human appetite control: a randomized crossover trial. Nutr J. 2014;13:49.



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Comparing the Effectiveness of Second-line Antidiabetic Medications on Cardiovascular Events in Patients with Type 2 Diabetes Mellitus

Comparing the Effectiveness of Second-line Antidiabetic Medications on Cardiovascular Events in Patients with Type 2 Diabetes Mellitus

By Mary R Dicklin, PhD and Kevin C Maki, PhD, CLS, FNLA


Cardiovascular disease is the leading cause of morbidity and mortality among patients with type 2 diabetes (T2D).1  Metformin is widely recommended as first-line therapy, but metformin alone may be inadequate for achieving glycemic control, or may not be tolerated, in which case clinicians have several second-line antidiabetic medication (ADM) prescription options.2  The second-line ADMs include sulfonylureas (SFUs), thiazolidinediones (TZDs), insulin, glucagon-like peptide 1 (GLP-1) receptor agonists, sodium-glucose-cotransporter 2 (SGLT-2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors.3  Understanding how these ADMs differ in their effects on cardiovascular outcomes may assist clinicians in preventing comorbidities in patients with diabetes.


Results were recently published from a large, retrospective cohort study that examined major adverse cardiovascular events among insured adults with T2D who had recently started therapy with a second-line ADM after either taking metformin alone or not having received prior ADM.4  Nationwide U.S. administrative claims data were used from 2011-2015.  The primary outcome of the study was time to first cardiovascular event (defined as the composite of hospitalization for congestive heart failure, stroke, ischemic heart disease or peripheral artery disease) after starting a second-line ADM.  Patients were censored after either their first cardiovascular event, discontinuation of insurance coverage, transition of medical claims data coding from the International Classification of Diseases 9th revision to the 10th revision, or two years of follow up.


Among the 132,737 adults evaluated in this study, SFUs were used by 47.6%, DPP-4 inhibitors by 21.8%, basal insulin by 12.2%, GLP-1 receptor agonists by 8.6%, TZDs by 5.6% and SGLT-2 inhibitors by 4.3%.4  During the 169,384 person-years of follow-up there were 3480 incident cardiovascular events.  After adjusting for patient, prescriber and health plan characteristics, the risk of composite cardiovascular events according to second-line ADM was determined.  DPP-4 inhibitors were considered to have a neutral effect on cardiovascular outcomes, based on previous clinical trial evidence.5-7  Thus, DPP-4 inhibitor use was the referent (1.0) in the Cox proportional hazard regression analysis.4  The hazard ratios (95% confidence intervals) were:

  • DPP-4 inhibitors: 1.00 (reference)
  • GLP-1 receptor agonists: 0.78 (0.63-0.96)
  • SGLT-2 inhibitors: 0.81 (0.57-1.53)
  • TZDs: 0.92 (0.76-1.11)
  • SFUs: 1.36 (1.23-1.49)
  • Basal insulin: 2.03 (1.81-2.27)


Higher cardiovascular risk was associated with use of SFUs or basal insulin.  The risk associated with GLP-1 receptor agonist use was lower than with DPP-4 inhibitor use, but this finding was not statistically significant in all of the sensitivity analyses.  The risks associated with SGLT-2 inhibitors and TZDs were not significantly different from DPP-4 inhibitors.


Recent randomized clinical trials that have evaluated the cardiovascular risk associated with newer ADMs have also suggested reduced cardiovascular events.8,9  Unlike those randomized trials, in which most of the participants already had cardiovascular disease, just 5.5% of participants in this observational study had a history of prior cardiovascular events, although cardiovascular risk factors, such as dyslipidemia (61.6%) and hypertension (70.1%), were present in the majority of subjects.


In summary, these results suggest that, with regard to managing cardiovascular comorbidity in their patients with T2D, after metformin, clinicians may consider prescribing any of the newer ADMs (i.e., GLP-1 receptor agonists, SGLT-2 inhibitors and DPP-4 inhibitors) that were shown to be similarly associated with lower cardiovascular risk, instead of SFUs or basal insulin, which were associated with greater cardiovascular risk.



  1. American Diabetes Association. 10. Cardiovascular disease and risk management: Standard of medical care in diabetes – 2019. Diabetes Care. 2019;42(Suppl 1):S102-S123.
  2. American Diabetes Association. 3. Prevention or delay of type 2 diabetes: Standards of medical care in diabetes – 2019. Diabetes Care. 2019;42(Suppl 1):S29-S33.
  3. Thrasher J. Pharmacologic management of type 2 diabetes mellitus: available therapies. Am J Cardiol. 2017;120:S4-S16.
  4. O’Brien MJ, Karam SL, Wallia A, et al. Association of second-line antidiabetic medications with cardiovascular events among insured adults with type 2 diabetes. JAMA Network Open. 2018;1:e1816125.
  5. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317-1326.
  6. Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373:232-242.
  7. White WB, Kupfer S, Zannad F, et al. Cardiovascular mortality in patients with type 2 diabetes and recent acute coronary syndromes from the EXAMINE trial. Diabetes Care. 2016;39:1267-1273.
  8. Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2018; Epub ahead of print.
  9. Sposito AC, Berwanger O, de Carvalho LSG, Saraiva JFK. GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data. Cardiovasc Diabetol. 2018;17:157.
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