Ruchi Mathur

Use of metformin in polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) have a myriad of phenotypic and clinical features that may guide therapeutic options for metabolic protection and ovulation induction. The use of metformin may prove beneficial in a subset of the population of women with PCOS. Hyperinsulinemia, as demonstrated by elevated insulin levels on a 2-hour 75-g load glucose tolerance test, is an important parameter in deciding whether or not to initiate metformin therapy to women with PCOS with the hope of preventing or delaying the onset of type 2 diabetes mellitus (DM). Cardiovascular risk factors including markers of subclinical inflammation, and dyslipidemia may also be improved by metformin therapy. For ovulation induction, metformin is not as effective as clomiphene citrate as first-line therapy for women with PCOS. There are no clear data to suggest that metformin reduces pregnancy loss or improves pregnancy outcome in PCOS, and it is currently recommended that metformin be discontinued with the first positive pregnancy test result, unless there are other medical indications (eg, type 2 DM). This review addresses practical management guidelines for the uses of metformin in women with PCOS.

Gynecomastia: Pathomechanisms and Treatment Strategies

Gynecomastia is common in adolescents and adults, and reflects an underlying imbalance in hormonal physiology in which there is an increase in estrogen action relative to androgen action at the breast tissue level. Most patients have persistent pubertal gynecomastia or breast glandular enlargement from medications, age-related reduction in testicular function, or idiopathic causes. Gynecomastia must be differentiated from pseudogynecomastia due to increased breast adipose tissue, as well as from breast carcinoma. The evaluation of the causes of gynecomastia can be accomplished through history, physical examination and a few laboratory tests. Painful gynecomastia of recent onset may respond to antiestrogen therapy. Surgical removal is the mainstay for long-standing gynecomastia or glandular enlargement that is unresponsive to medical therapy.

Methane and Hydrogen Positivity on Breath Test Is Associated With Greater Body Mass Index and Body Fat

CONTEXT Colonization of the gastrointestinal tract with methanogenic archaea (methanogens) significantly affects host metabolism and weight gain in animal models, and breath methane is associated with a greater body mass index (BMI) among obese human subjects. OBJECTIVE The objective of the study was to characterize the relationship between methane and hydrogen on breath test (as a surrogate for colonization with the hydrogen requiring methanogen, Methanobrevibacter smithii), body weight, and percent body fat in a general population cohort. DESIGN AND SUBJECTS This was a prospective study (n = 792) of consecutive subjects presenting for breath testing. SETTING The study was conducted at a tertiary care center. OUTCOME MEASUREMENTS BMI and percent body fat were measured. RESULTS Subjects were classified into 4 groups based on breath testing: normal (N) (methane <3 ppm and hydrogen <20 ppm at or before 90 minutes); hydrogen positive only (H+) [methane <3 ppm and hydrogen ≥20 ppm); methane positive only (M+) (methane ≥3 ppm and hydrogen <20 ppm), or methane and hydrogen positive (M+/H+) (methane ≥3 ppm and hydrogen ≥20 ppm]. There were significant differences in age but not in gender across the groups. After controlling for age as a confounding variable, M+/H+ subjects had significantly higher BMI than other groups (N: 24.1 ± 5.2 kg/m(2); H+: 24.2 ± 4.5 kg/m(2); M+: 24.0 ± 3.75 kg/m(2); M+/H+: 26.5 ± 7.1 kg/m(2), P < .02) and also had significantly higher percent body fat (N: 28.3 ± 10.0%; H+: 27.5 ± 9.0%; M+: 28.0 ± 8.9%; M+/H+; 34.1 ± 10.9%, P < .001). CONCLUSIONS The presence of both methane and hydrogen on breath testing is associated with increased BMI and percent body fat in humans. We hypothesize that this is due to colonization with the hydrogen-requiring M smithii, which affects nutrient availability for the host and may contribute to weight gain.

Oral contraceptive pill use and abnormal menstrual cycles in women with severe condylar resorption: A case for low serum 17β-estradiol as a major factor in progressive condylar resorption

INTRODUCTION Progressive condylar resorption has been described for many years. Because condylar resorption favors women over men, many have thought that a prominent systemic factor for the pathogenesis of this disease might be related to sex hormones. METHODS Over a 3-year period, 27 women without autoimmune disease came to our office for orthognathic surgical correction of their skeletal deformity secondary to severe condylar resorption. They all showed radiographic evidence of severe condylar resorption. Sex hormone dysfunction was evaluated, and midcycle serum levels of 17beta-estradiol were measured. Use of exogenous hormones was also documented. RESULTS Twenty-six of the 27 women with severe condylar resorption had either laboratory findings of low 17beta-estradiol or a history of extremely irregular menstrual cycles. Of the 27 women, 25 showed abnormally low levels of serum 17beta-estradiol at midcycle. Two subsets were identified in the group with low 17beta-estradiol. The first did not produce estrogen naturally (8 of 27), and the second had low 17beta-estradiol levels secondary to oral contraceptive pill (OCP) use (19 of 27). Of the 19 OCP users, all 19 reported that chin regression and open bite changes occurred after starting OCP use. Nine of the 19 reported these condylar resorption symptoms within the first 6 months of starting the OCP. CONCLUSIONS Whether induced by ethinyl estradiol birth control or by premature ovarian failure, low circulating 17beta-estradiol makes it impossible for the natural reparative capacity of the condyle to take place in the face of local inflammatory factors. This leads to cortical and medullary condylar lysis.

Pancreatic Steatosis and Its Relationship to β-Cell Dysfunction in Humans Racial and ethnic variations

OBJECTIVE To evaluate racial/ethnic differences in pancreatic triglyceride (TG) levels and their relationship to β-cell dysfunction in humans. RESEARCH DESIGN AND METHODS We studied black, Hispanic, and white adults who completed three research visits: screening and an oral glucose tolerance test; frequently sampled intravenous glucose tolerance tests for evaluation of β-cell function and insulin resistance; and proton magnetic resonance spectroscopy for evaluation of pancreatic and hepatic TG levels. RESULTS Pancreatic TG levels were higher in Hispanics and whites than in blacks (P = 0.006). Hepatic TG levels were highest in Hispanics (P = 0.004). Compensatory insulin secretion and disposition index were higher in blacks (P = 0.003 and P = 0.024, respectively). Insulin sensitivity was comparable between Hispanics and blacks and was lower than in whites (P = 0.005). In blacks, compensatory insulin secretion increased steeply with small increments in pancreatic TG levels (R2 = 0.45, slope = 247). In whites, the range of pancreatic TG levels was higher, and the slope was less steep than in blacks (R2 = 0.27, slope = 27). In Hispanics, pancreatic TG levels were similar to those of whites, but compensatory insulin secretion was described by a combination of pancreatic and hepatic TG levels and visceral fat mass ( R2 = 0.32). CONCLUSIONS In a multiethnic sample of adults with mild obesity and without diabetes, we found striking ethnic differences in the levels of pancreatic TGs and in the relationship between pancreatic TGs and β-cell dysfunction. Our data implicate pancreatic TG content measured by proton magnetic resonance spectroscopy as a noninvasive novel biomarker for pancreatic β-cell dysfunction, especially in the Hispanic population.

Role of the Gut Microbiome in Obesity and Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) and obesity represent two of the biggest global health challenges of this century and are associated with significant comorbidities and healthcare costs. Although multiple factors undoubtedly contribute to the development and progression of DM and obesity, research over the last decade has demonstrated that the microbes that colonize the human gut may play key contributory roles. Gut microbes are now known to codevelop with the human host and are strongly influenced by mode of birth and early diet and nutrition, as well as environmental and other factors including antibiotic exposure. Gut microbes contribute to human health through roles in polysaccharide breakdown, nutrient absorption, inflammatory responses, gut permeability, and bile acid modification. Numerous studies have suggested that disruptions in the relative proportions of gut microbial populations may contribute to weight gain and insulin resistance, including alterations in Gammaproteobacteria and Verrucomicrobia and the ratios of Firmicutes to Bacteroidetes in weight gain and possible alterations in butyrate-producing bacteria such as Faecalibacterium prausnitzii in DM. In addition, it has been shown that the methanogenic Archaea may contribute to altered metabolism and weight gain in the host. However, the majority of studies are performed with stool or colonic samples and may not be representative of the metabolically active small intestine. Studies predominantly in rodent models are beginning to elucidate the mechanisms by which gut microbes contribute to DM and obesity, but much remains to be learned before we can begin to approach targeted treatments.

Efficacy of the glucagon‐like peptide‐1 agonist exenatide in the treatment of short bowel syndrome

Background  Short bowel syndrome (SBS) is a serious clinical disorder characterized by diarrhea and nutritional deprivation. Glucagon‐like peptide‐1 (GLP‐1) is a key hormone, produced by L‐cells in the ileum, that regulates proximal gut transit. When extensive ileal resection occurrs, as in SBS, GLP‐1 levels may be deficient. In this study, we test whether the use of GLP‐1 agonist exenatide can improve the nutritional state and intestinal symptoms of patients with SBS.

Obesity and the microbiome

Obesity constitutes a significant and rapidly increasing public health challenge and is associated with significant co-morbidities and healthcare costs. Although undoubtedly multifactorial, research over the last decade has demonstrated that the microbes that colonize the human gut may contribute to the development of obesity through roles in polysaccharide breakdown, nutrient absorption, inflammatory responses and gut permeability. Studies have consistently shown that the Firmicutes to Bacteroidetes ratio, in particular, is increased in obesity and reduces with weight loss. In addition, we and others have shown that the methanogenic Archaea may also contribute to altered metabolism and weight gain in the host. However, much remains to be learned about the roles of different gut microbial populations in weight gain and obesity and the underlying mechanisms before we can begin to approach targeted treatments.

Novel therapeutic strategies for the treatment of type 2 diabetes.

Diabetes mellitus is the most common endocrine disease, accounting for over 200 million people affected worldwide. It is characterized by a lack of insulin secretion and/or increased cellular resistance to insulin, resulting in hyperglycemia and other metabolic disturbances. People with diabetes suffer from increased morbidity and premature mortality related to cardiovascular, microvascular and neuropathic complications. The Diabetes Control and Complication Trial (DCCT) has convincingly demonstrated the relationship of hyperglycemia to the development and progression of complications and showed that improved glycemic control reduced these complications. Although the DCCT exclusively studied patients with Type 1 diabetes, there is ample evidence to support the belief that the same relationship between metabolic control and clinical outcome exists in patients with Type 2 diabetes. Therefore, a major effort should be made to develop and implement more effective treatment regimes. This article reviews those novel drugs that have been recently introduced for the management of Type 2 diabetes, or that have reached an advanced level of study and will soon be proposed for preliminary clinical trials. They include: (i) compounds that promote the synthesis/secretion of insulin by the beta-cell; (ii) inhibitors of the alpha-glucosidase activity of the small intestine; (iii) substances that enhance the action of insulin at the level of the target tissues; and (iv) inhibitors of free fatty acid oxidation.

Gas and the Microbiome

Humans are host to trillions of microbial colonizers that contribute significantly to human health and disease. Advances in sequencing and other technologies have facilitated dramatic advances in our knowledge of the types and number of organisms colonizing different areas of the body, and while our knowledge of the roles played by the different bacteria, fungi, and archaea has increased dramatically, there remains much to uncover. The microbes that colonize the human gut contribute to vitamin biosynthesis, immune modulation, and the breakdown of otherwise indigestible foods for nutrient harvest. Bacteria and archaea produce various gases as by-products of fermentation, and it is becoming increasingly understood that these gases have both direct and indirect effects on the gut, and may also be used as diagnostic markers, e.g., hydrogen production as measured by breath testing can be used to diagnose bacterial overgrowth. In this article, we review the roles and effects of hydrogen (H2), methane (CH4) and hydrogen sulfide (H2S) in the human gut.