XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

1. Type 1 diabetes (due to b-cell destruction, usually leading to absolute insulin deficiency) 2. Type 2 diabetes (due to a progressive insulin secretory defect on the background of insulin resistance) 3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes) 4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young [MODY]), diseases of the exocrine pancreas (such as cystic fibrosis), and drugor chemical-induced diabetes (such as in the treatment of HIV/AIDS or after organ transplantation)

Classification and diagnosis of diabetes

Polycystic ovary syndrome (PCOS) represents a common endocrine-metabolic disorder disease with chronic low-grade inflammation and alteration of intestinal flora. Serving as functional food, flaxseed oil (FO), which is rich in plant-derived α-linolenic acid of omega-3 polyunsaturated fatty acids, has been proven to benefit for chronic metabolic diseases. However, the exact role of dietary FO on PCOS remains largely unclear. In the present study, 6-week-old female Sprague-Dawley rats were randomly divided into four groups (eight rats/group), including (a) pair-fed (PF) control (CON) group (PF/CON), (b) FO-fed CON group (FO/CON), (c) PF with letrozole-induced PCOS model (MOD) group (PF/MOD), and (d) FO-fed MOD group (FO/MOD). All rats were fed a standard diet. After 3 weeks of modeling and subsequent 8 weeks of treatment, the rats in diverse groups were euthanized and associated indications were investigated. The results showed that dietary FO ameliorated the disorder of estrous cycle and ovarian morphology. In parallel, dietary FO improved the sex steroid hormone disturbance (luteinizing hormone/follicle-stimulating hormone, estrogen, testosterone, and progesterone), body weights, dyslipidemia, and insulin resistance. Moreover, FO treatment improved plasma and ovary inflammatory interleukin (IL)-1β, IL-6, IL-10, and IL-17A, tumor necrosis factor-α, and monocyte chemoattractant protein-1. Additionally, FO intervention significantly modulated the composition of gut microbiota and vaginal microbiota by increasing the abundances of Allobaculum, Lactobacillus, Butyrivibrio, Desulfovibrio, Bifidobacterium, Faecalibacterium, Parabacteroides as well as decreasing the abundances of Actinobacteria, Bacteroides, Proteobacteria, and Streptococcus, the ratio of Firmicutes/Bacteroidetes. A decrease in plasma lipopolysaccharide level and an increase in short-chain fatty acids, including acetic acid, propionic acid, butyric acid and pentanoic acid, were determined after dietary FO supplementation. Correlation analysis revealed close relationships among sex steroid hormones, inflammation, and gut/vaginal microbiota. Collectively, this study demonstrated that dietary FO ameliorated PCOS through the sex steroid hormones-microbiota-inflammation axis in rats, which may contribute to the understanding of pathogenesis and potentially serve as an inexpensive intervention in the control of PCOS.

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Dietary α-Linolenic Acid-Rich Flaxseed Oil Exerts Beneficial Effects on Polycystic Ovary Syndrome Through Sex Steroid Hormones-Microbiota-Inflammation Axis in Rats

Polycystic ovary syndrome (PCOS) is widely accepted as the most common endocrine abnormality in women of childbearing age and may be accompanied by dyslipidemia, hyperandrogenism, hyperinsulinemia, oxidative stress and infertility. Dyslipidemia is now known to play an important role in the development of PCOS. Lipid abnormalities, including elevated low-density lipoprotein and triglyceride levels and reduced high-density lipoprotein levels, are often found in women with PCOS and play an important role in PCOS; therefore, we summarize the effect of lipid abnormalities on hyperandrogenism, insulin resistance, oxidative stress and infertility in PCOS and review the effects of common lipid-lowering drugs on patients with PCOS. The purpose of this article is to elucidate the mechanisms of lipid metabolism abnormalities in the development of PCOS.

Dyslipidemia involvement in the development of polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is the most common endocrine–metabolic disorder affecting a vast population worldwide; it is linked with anovulation, mitochondrial dysfunctions and hormonal disbalance. Mutations in mtDNA have been identified in PCOS patients and likely play an important role in PCOS aetiology and pathogenesis; however, their causative role in PCOS development requires further investigation. As a low-grade chronic inflammation disease, PCOS patients have permanently elevated levels of inflammatory markers (TNF-α, CRP, IL-6, IL-8, IL-18). In this review, we summarise recent data regarding the role of mtDNA mutations and mitochondrial malfunctions in PCOS pathogenesis. Furthermore, we discuss recent papers dedicated to the identification of novel biomarkers for early PCOS diagnosis. Finally, traditional and new mitochondria-targeted treatments are discussed. This review intends to emphasise the key role of oxidative stress and chronic inflammation in PCOS pathogenesis; however, the exact molecular mechanism is mostly unknown and requires further investigation.

https://www.mdpi.com/1422-0067/22/8/3923/pdf

Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome.

Objective This study explores the role of anti-Mullerian hormone (AMH) and LH/FSH ratio in diagnosis of polycystic ovary syndrome (PCOS). Methods In this multicentre cross-sectional descriptive study, a total of 863 infertile women between 18 and 45 years were evaluated at three infertility centres in Vietnam and were recruited from June 2016 to June 2017. The patients were classified into two groups: Group I included 441 patients with PCOS (based on Rotterdam criteria consensus) and Group II included 422 non-PCOS women. Diagnosis of PCOS was established based on Rotterdam 2003 consensus, and exclusion criteria were ovarian disease (ovary cyst/tumour), history of ovarian surgery and ovarian failure. Results At an optimum cut-off level of 32.79 pmol/L, AMH showed sensitivity and specificity of 78.50% and 75.83%, respectively, with the AUC 0.852 (95% CI: 0.826-0.875). The LH/FSH ratio had a similar AUC at the optimum cut-off of 1.33 (AUC = 0.867, 95% CI 0.842-0.889), which demonstrated a similar diagnosis value to AMH (P = 0.340). By using multiple logistic regression analysis, 1 ng/mL increase in AMH levels was associated with an increased risk of PCOS (OR = 1.63, 95% CI: 1.506-1.764; P < 0.001). Similarly, one unit increase in LH/FSH ratio was associated with 14.433 times increased (95% CI: 9.302-22.395; P < 0.001) risk of PCOS. There were no significant differences between values of AMH and LH/FSH ratio in PCOS diagnosis, as the difference between the two AUCs was 0.013, 95% CI: -0.024 to 0.028 and P = 0.897. Conclusion The value of serum AMH concentration has been found not significantly superior to LH/FSH ratio in PCOS diagnosis. Although these biomarkers separately are not adequate for PCOS diagnosis based on their own value, the combination of different endocrine factors including AMH, LH and LH/FSH ratio together with BMI and other anthropometric and clinical characteristics may offer extra value to establish the diagnosis of PCOS.

Exploration of the role of anti-Mullerian hormone and LH/FSH ratio in diagnosis of polycystic ovary syndrome.

Aim This study aimed to evaluate the unique phenotype of the Vietnamese polycystic ovarian syndrome (PCOS) population. Methods In this multicenter cross-sectional descriptive study, a total of 901 reproductive-age women were recruited at three medical centers in Vietnam from June 2016 to May 2018. Group I included 479 patients with PCOS (Rotterdam 2003 consensus) and Group II included 422 non-PCOS women, consisted of women with regular menstrual cycle, collected at the same time of PCOS recruitment, without ovarian disease or ovarian failure. Main outcome measures were anthropomorphic, serum hormone, ultrasound and physical characteristics of PCOS. Results The Vietnamese PCOS population was lean, but with a higher weight and body mass index compared to controls. About 34.4% of PCOS subjects had hirsutism, primarily confined to the leg, arm and pubis. The PCOS population had higher serum luteinizing hormone (LH), LH : follicle stimulating hormone ratio, anti-Mullerian hormone and testosterone. The PCOS population had double the ovarian volume compared to controls. PCOS subjects had no increase in metabolic disease history and had on average optimal serum markers for low metabolic disease risk. Group D (O + polycystic ovary morphology [PCOM]) was the most prevalent phenotype noted in our Vietnamese PCOS cohort (67.6%). Modified Ferriman-Gallwey, levels of LH, testosterone and anti-Mullerian hormone were highest in Group A (O + H + PCOM) and lowest in Group D (O + PCOM). Conclusion The Vietnamese PCOS population is characterized by a lean body type, nonfacial hirsutism, anovulatory, enlarged ovaries and typical PCOS serum hormone markers, low risk factors for metabolic syndrome. Nonclassical phenotypes for PCOS were more frequent than the classic phenotype.

Defining polycystic ovary syndrome phenotype in Vietnamese women.

Background Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies among reproductive-age women. Its metabolic features often overlap with those associated with metabolic syndrome (MS) and insulin resistance syndrome (IRS). The objective of this study was to determine the prevalence and predictors of MS and IRS in infertile Vietnamese women with PCOS. Methods A cross-sectional study was conducted at a tertiary fertility centre at Hue University Hospital from June 2016 to November 2017. A total of 441 infertile women diagnosed with PCOS based on the revised 2003 Rotterdam consensus criteria were enrolled. MS and IRS were defined based on the National Heart, Lung, and Blood Institute/American Heart Association Adult Treatment Panel III 2005 and American College of Endocrinology IRS 2003 criteria, respectively. Complete clinical and biochemical measurements of 318 women were available for analysis. Independent predictors of MS and IRS were identified using multivariate logistic regression. Results The overall prevalence of MS and IRS in women with PCOS was 10.4% and 27.0%, respectively. We identified older age (>30 years) and obesity as independent predictors of MS and IRS. Elevated anti-Mullerian hormone levels increased the risk of IRS, but not that of MS. Conclusion MS and IRS are prevalent disorders among infertile Vietnamese women with PCOS. PCOS is not solely a reproductive problem. Screening and early intervention for MS and/or IRS based on anthropometric, metabolic, and reproductive hormone risk factors should be an integral part of fertility care.

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Metabolic Syndrome and Insulin Resistance Syndrome among Infertile Women with Polycystic Ovary Syndrome: A Cross-Sectional Study from Central Vietnam.

Metabolic disorders in infertile women with polycystic ovary syndrome

Objectives: This study aimed to assess the impact of Inositol on the clinical characteristics, endocrine and metabolic profiles of infertile PCOS patients from Vietnam. 
Methods: From June 2018 to June 2022, a clinical trial was undertaken at the Center for Reproductive Endocrinology and Infertility on infertile women aged 18 to 40 with PCOS. The clinical, endocrine, and metabolic features of these individuals were assessed before and after 3 months of treatment with 2g of Inositol per day. Natural pregnancy rates, adverse effects, and tolerance of Inositol have also been recorded. 
Results: After three months of Inositol treatment, 18.2% of patients with oligomenorrhea experienced regular menstruation. Inositol therapy dramatically lowered hips circumference and Testosterone levels, but had no effect on other clinical characteristics, endocrine profiles, or metabolic profiles. In the overweight and obese group, weight, BMI, waist and hip circumferences decreased dramatically while regular menstrual cycles were improving in non overweight/ obse group. 9.4% of patients reported experiencing side effects; despite this, 100% of women tolerated Inositol and maintained treatment. 18.9% of them attained pregnancy, which resulted in 17% live births. 
Conclusion: Inositol appears to increase menstrual cycle regularity and decrease Testosterone levels; resulting in a clinical pregnancy rate of 18.9% and a live birth rate of 17.0%. Inositol appears to be more beneficial in improving weight, BMI, waist and híp circumference in the obese and overweight population.

Viet Nguyen Sa Le

Papers

Exploration of the role of anti-Mullerian hormone and LH/FSH ratio in diagnosis of polycystic ovary syndrome.

Defining polycystic ovary syndrome phenotype in Vietnamese women.

Metabolic Syndrome and Insulin Resistance Syndrome among Infertile Women with Polycystic Ovary Syndrome: A Cross-Sectional Study from Central Vietnam.

Metabolic disorders in infertile women with polycystic ovary syndrome

Effectiveness of Inositol on clinical features, endocrine and metabolic profiles in infertile patients with polycystic ovary syndrome