Dr. Ron’s Research Review – January 8, 2019

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This week’s research review focuses on hyperinsulinemia.

Hyperinsulinemia is excess levels of insulin relative to the level of glucose in the blood. Hyperinsulinemia is often associated with type 2 diabetes, and is most often caused by insulin resistance. (Thomas et al., 2019)
Hyperinsulinemia as determined by glucose/insulin tolerance identified an etiologic relationship to idiopathic Menière's disease. Proctor identified hyperinsulinemia in subjective idiopathic tinnitus (SIT). Hyperinsulinemia and migraine with tinnitus and/or vertigo were also correlated. (Kraft, 1995)

Myo-Inositol for PCOS

Myo-inositol administration improves reproductive axis functioning in PCOS patients reducing the hyperinsulinemic state that affects LH secretion. (Genazzani et al., 2008)
A study published in Gynecological Endocrinology evaluated the effects the administration of myo-inositol (MYO) on hormonal parameters in a group of PCOS patients. The University of Modena and Reggio Emilia, Italy conducted the study.
Twenty overweight PCOS patients underwent hormonal evaluations and an oral glucose tollerance test (OGTT) before and after 12 weeks of therapy. Group A (n = 10) received myo-inositol 2 gr. plus folic acid 200 mug every day; Group B (n = 10): folic acid 200 mug every day).
After 12 weeks of myo-inositol administration plasma LH, PRL, T, insulin levels and LH/FSH resulted significantly reduced. Insulin sensitivity, expressed as glucose-to-insulin ratio and HOMA index resulted significantly improved after 12 weeks of treatment. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic subjects. No changes occurred in the patients treated with folic acid.
Myo-inositol administration improves reproductive axis functioning in PCOS patients reducing the hyperinsulinemic state that affects LH secretion. (Genazzani et al., 2008)

Folate and Vitamin B12 with Metabolic Syndrome

Folate and vitamin B12 treatment improved insulin resistance and endothelial dysfunction, along with decreasing homocysteine levels, in patients with metabolic syndrome. (Setola et al., 2004)
A study published in the European Journal of Endocrinology examined whether a folate and vitamin B12 treatment, aimed at decreasing homocysteine levels, might ameliorate insulin resistance and endothelial dysfunction in patients with metabolic syndrome according to the National Cholesterol Education Pro- gram–Adult Treatment Panel-III criteria and (b) to evaluated whether, under these metabolic conditions, there is a relationship between hyperhomocysteinemia and insulin resistance. The University of Milano-Bicocca, Milan, Italy conducted the study.
A double-blind, parallel, identical placebo-drug, randomized study was performed for 2 months in 50 patients. Patients were randomly allocated to two groups. In group 1, patients were treated with diet plus placebo for 2 months. In group 2, patients were treated with diet plus placebo for 1 month, followed by diet plus folic acid (5 mg/day) plus vitamin B12 (500 microg/day) for another month.
In group 2, folate treatment significantly decreased homocysteine levels by 27.8% (12.2+/-1.2 vs 8.8+/-0.7 micromol/l; P<0.01). A significant decrement was observed for insulin levels (19.9+/-1.7 vs 14.8+/-1.6 microU/ml; P<0.01) accompanied by a 27% reduction in the homeostasis model assessment levels. A positive relationship was found between the decrement of homocysteine and insulin levels (r=0.60; P<0.002). In parallel, endothelial dysfunction significantly improved in the treated group, since post-ischemic maximal hyperemic vasodilation increased by 29.8% and cGMP by 13.6% while asymmetrical dimethylarginine levels decreased by 21.7%. On the contrary, in group 1 patients, treated with placebo, no changes were shown in any of the variables.
Folate and vitamin B12 treatment improved insulin resistance and endothelial dysfunction, along with decreasing homocysteine levels, in patients with metabolic syndrome, suggesting that folic acid has several beneficial effects on cardiovascular disease risk factors. (Setola et al., 2004)

Chili Powder for Women with Gestational Diabetes 

Capsaicin-containing chili improved postprandial hyperglycemia, hyperinsulinemia, and fasting lipid disorders in women with gestational diabetes mellitus. (Yuan et al., 2016)
A study published in Clinical Nutrition determined the effect of capsaicin supplementation on blood glucose, lipid metabolism and pregnancy outcomes in women with gestational diabetes mellitus. The Southwest Hospital, Third Military Medical University, China conducted the study.
Forty-four pregnant women with gestational diabetes mellitus at 22-33 gestational weeks were randomly assigned to the capsaicin group (5 mg/d of capsaicin) or to the placebo group (0 mg/d of capsaicin) for 4 weeks in a randomized, double-blind, placebo-controlled trial. Women were instructed to consume 0.625 g of chili powder twice daily (total: 1.25 g per day) at lunch and dinner, respectively, for 4 weeks. In the capsaicin and the placebo groups, the chili powders were made from crushed yanjiao 425 (one type of pop pepper; capsaicin content 4 mg/g) and xingjiang sweet (Capsicum annuum L, without capsaicin), respectively. The concentrations of fasting plasma glucose and serum insulin, 2-h postprandial plasma glucose (2-h PG) and serum insulin (2-h INS), and fasting serum lipids, liver and kidney function parameters, and calcitonin gene-related peptide (CGRP) were measured at 0 and 4 weeks. The maternal and neonatal outcomes were also recorded. Forty-two women completed the trial.
Compared to the placebo group, 2-h PG and 2-h INS concentrations and 2-h postprandial HOMA-IR (2-h HOMA-IR) levels, and the fasting serum total cholesterol and triglycerides concentrations significantly decreased in the capsaicin group after treatment (P < 0.05). Moreover, the fasting serum apolipoprotein B and CGRP concentrations significantly increased in the capsaicin group (P < 0.05). The changes in the 2-h PG and 2-h INS concentrations and in the 2-h HOMA-IR were negatively correlated with the change in the serum CGRP concentration (P < 0.05). Furthermore, the incidence of large-for-gestational-age (LGA) newborns was significantly lower in the capsaicin group than in the placebo group (P = 0.022).
Capsaicin-containing chili supplementation regularly improved postprandial hyperglycemia and hyperinsulinemia as well as fasting lipid metabolic disorders in women with gestational diabetes mellitus, and it decreased the incidence of LGA newborns. (Yuan et al., 2016)

Dr. Ron

 

Articles

Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome.
            (Genazzani et al., 2008) Download
OBJECTIVE:  To evaluate the effects the administration of myo-inositol (MYO) on hormonal parameters in a group of PCOS patients. DESIGN:  Controlled clinical study. SETTING:  PCOS patients in a clinical research environment. PATIENTS:  20 overweight PCOS patients were enrolled after informed consent. INTERVENTIONS:  All patients underwent hormonal evaluations and an oral glucose tollerance test (OGTT) before and after 12 weeks of therapy (Group A (n = 10): myo-inositol 2 gr. plus folic acid 200 mug every day; Group B (n = 10): folic acid 200 mug every day). Ultrasound examinations and Ferriman-Gallwey score were also performed. MAIN OUTCOME MEASURES:  Plasma LH, FSH, PRL, E2, 17OHP, A, T, glucose, insulin, C peptide concentrations, BMI, HOMA index and glucose-to-insulin ratio. RESULTS:  After 12 weeks of MYO administration plasma LH, PRL, T, insulin levels and LH/FSH resulted significantly reduced. Insulin sensitivity, expressed as glucose-to-insulin ratio and HOMA index resulted significantly improved after 12 weeks of treatment. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic subjects. No changes occurred in the patients treated with folic acid. CONCLUSIONS:  Myo-inositol administration improves reproductive axis functioning in PCOS patients reducing the hyperinsulinemic state that affects LH secretion.


 

Hyperinsulinemia: The Common Denominator of Subjective Idiopathic Tinnitus and Other Idiopathic Central and Peripheral Neurootologic Disorders.
            (Kraft, 1995) Download
Hyperinsulinemia as determined by glucose/insulin tolerance identified an etiologic relationship to idiopathic Menière's disease. This was subsequently concurred with internationally by others. Proctor identified hyperinsulinemia in Subjective Idiopathic Tinnitus (SIT). Hyperinsulinemia and migraine with tinnitus and/or vertigo were also correlated.

Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia.
            (Setola et al., 2004) Download
OBJECTIVE:  The purpose of this study was (a) to study whether a folate and vitamin B12 treatment, aimed at decreasing homocysteine levels, might ameliorate insulin resistance and endothelial dysfunction in patients with metabolic syndrome according to the National Cholesterol Education Program-Adult Treatment Panel-III criteria and (b) to evaluate whether, under these metabolic conditions, there is a relationship between hyperhomocysteinemia and insulin resistance. DESIGN AND METHODS:  A double-blind, parallel, identical placebo-drug, randomized study was performed for 2 months in 50 patients. Patients were randomly allocated to two groups. In group 1, patients were treated with diet plus placebo for 2 months. In group 2, patients were treated with diet plus placebo for 1 month, followed by diet plus folic acid (5 mg/day) plus vitamin B12 (500 microg/day) for another month. RESULTS:  In group 2, folate treatment significantly decreased homocysteine levels by 27.8% (12.2+/-1.2 vs 8.8+/-0.7 micromol/l; P<0.01). A significant decrement was observed for insulin levels (19.9+/-1.7 vs 14.8+/-1.6 microU/ml; P<0.01) accompanied by a 27% reduction in the homeostasis model assessment levels. A positive relationship was found between the decrement of homocysteine and insulin levels (r=0.60; P<0.002). In parallel, endothelial dysfunction significantly improved in the treated group, since post-ischemic maximal hyperemic vasodilation increased by 29.8% and cGMP by 13.6% while asymmetrical dimethylarginine levels decreased by 21.7%. On the contrary, in group 1 patients, treated with placebo, no changes were shown in any of the variables. CONCLUSIONS:  Folate and vitamin B12 treatment improved insulin resistance and endothelial dysfunction, along with decreasing homocysteine levels, in patients with metabolic syndrome, suggesting that folic acid has several beneficial effects on cardiovascular disease risk factors.


 

Hyperinsulinemia: An Early Indicator of Metabolic Dysfunction.
            (Thomas et al., 2019) Download
Hyperinsulinemia is strongly associated with type 2 diabetes. Racial and ethnic minority populations are disproportionately affected by diabetes and obesity-related complications. This mini-review provides an overview of the genetic and environmental factors associated with hyperinsulinemia with a focus on racial and ethnic differences and its metabolic consequences. The data used in this narrative review were collected through research in PubMed and reference review of relevant retrieved articles. Insulin secretion and clearance are regulated processes that influence the development and progression of hyperinsulinemia. Environmental, genetic, and dietary factors are associated with hyperinsulinemia. Certain pharmacotherapies for obesity and bariatric surgery are effective at mitigating hyperinsulinemia and are associated with improved metabolic health. Hyperinsulinemia is associated with many environmental and genetic factors that interact with a wide network of hormones. Recent studies have advanced our understanding of the factors affecting insulin secretion and clearance. Further basic and translational work on hyperinsulinemia may allow for earlier and more personalized treatments for obesity and metabolic diseases.

Capsaicin-containing chili improved postprandial hyperglycemia, hyperinsulinemia, and fasting lipid disorders in women with gestational diabetes mellitus and lowered the incidence of large-for-gestational-age newborns.
            (Yuan et al., 2016) Download
BACKGROUND & AIMS:  Gestational diabetes mellitus (GDM) may increase the future health risks of women and their offspring. The aim of this study was to determine the effect of capsaicin supplementation on blood glucose, lipid metabolism and pregnancy outcomes in women with GDM. METHODS:  Forty-four pregnant women with GDM at 22-33 gestational weeks were randomly assigned to the capsaicin group (5 mg/d of capsaicin) or to the placebo group (0 mg/d of capsaicin) for 4 weeks in a randomized, double-blind, placebo-controlled trial. The concentrations of fasting plasma glucose and serum insulin, 2-h postprandial plasma glucose (2-h PG) and serum insulin (2-h INS), and fasting serum lipids, liver and kidney function parameters, and calcitonin gene-related peptide (CGRP) were measured at 0 and 4 weeks. The maternal and neonatal outcomes were also recorded. RESULTS:  Forty-two women completed the trial. Compared to the placebo group, 2-h PG and 2-h INS concentrations and 2-h postprandial HOMA-IR (2-h HOMA-IR) levels, and the fasting serum total cholesterol and triglycerides concentrations significantly decreased in the capsaicin group after treatment (P < 0.05). Moreover, the fasting serum apolipoprotein B and CGRP concentrations significantly increased in the capsaicin group (P < 0.05). The changes in the 2-h PG and 2-h INS concentrations and in the 2-h HOMA-IR were negatively correlated with the change in the serum CGRP concentration (P < 0.05). Furthermore, the incidence of large-for-gestational-age (LGA) newborns was significantly lower in the capsaicin group than in the placebo group (P = 0.022). CONCLUSIONS:  Capsaicin-containing chili supplementation regularly improved postprandial hyperglycemia and hyperinsulinemia as well as fasting lipid metabolic disorders in women with GDM, and it decreased the incidence of LGA newborns.

 

References

Genazzani, AD, et al. (2008), ‘Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome.’, Gynecol Endocrinol, 24 (3), 139-44. PubMed: 18335328
Kraft (1995), ‘Hyperinsulinemia: The Common Denominator of Subjective Idiopathic Tinnitus and Other Idiopathic Central and Peripheral Neurootologic Disorders.’, Int Tinnitus J, 1 46-53. PubMed: 10753320
Setola, E, et al. (2004), ‘Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia.’, Eur J Endocrinol, 151 (4), 483-89. PubMed: 15476449
Thomas, DD, et al. (2019), ‘Hyperinsulinemia: An Early Indicator of Metabolic Dysfunction.’, J Endocr Soc, 3 (9), 1727-47. PubMed: 31528832
Yuan, LJ, et al. (2016), ‘Capsaicin-containing chili improved postprandial hyperglycemia, hyperinsulinemia, and fasting lipid disorders in women with gestational diabetes mellitus and lowered the incidence of large-for-gestational-age newborns.’, Clin Nutr, 35 (2), 388-93. PubMed: 25771490