Gonadotropins and Their Association with the Risk of Prediabetes and Type 2 Diabetes in Middle-Aged Postmenopausal Women

Recent studies have suggested that a low concentration of follicle-stimulating hormone (FSH) is associated with a higher prevalence of metabolic disturbances in postmenopausal women. In this study, we aim to evaluate the association between FSH, luteinizing hormone (LH), and LH/FSH ratio values and the risk of insulin resistance (HOMA-IR >2.0), prediabetes (IFG), and type 2 diabetes in a 5-year prospective study in postmenopausal women. 114 postmenopausal women were divided into 4 groups: group 1 (baseline and follow-up normoglycemic women), group 2 (normoglycemic women at baseline progressing to IFG), group 3 (women with baseline and follow-up IFG), and group 4 (women with baseline IFG progressing to diabetes). Baseline and follow-up anthropometric measurements and blood collections were performed. Serum/plasma was assayed for glucose, HDL-C, TG, C-reactive protein (CRP), 17beta-estradiol, estrone, insulin, thyroid-stimulating hormone (TSH), FSH, and LH. Homeostatic model assessment of insulin resistance (HOMA-IR) and LH/FSH ratios were calculated. The baseline concentrations of FSH and LH statistically decreased across all four groups (the highest concentrations in group 1 and the lowest in group 4; p<0.001). A logistic regression analysis showed that a 1 SD decrease in the z-score of FSH concentration is associated with a threefold increased risk of IFG and a fivefold increased risk of HOMA-IR of >2.0 and diabetes. The LH concentration had odds ratio (OR) values about two times lower than the FSH concentration. The ORs of the LH/FSH ratio were only significant for IFG. In conclusion, FSH concentration is strongly associated with insulin resistance, prediabetes, and diabetes in postmenopausal women with normal or impaired fasting glucose. LH and the LH/FSH ratio are also related to metabolic disturbances after menopause, yet to a lesser extent.

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Elevated circulating follistatin associates with an increased risk of type 2 diabetes

Nature Communications ◽

10.1038/s41467-021-26536-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Chuanyan Wu ◽

Yan Borné ◽

Rui Gao ◽

Maykel López Rodriguez ◽

William C. Roell ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Adipose Tissue ◽

Genome Wide Association Study ◽

Regulatory Protein ◽

Alcoholic Fatty Liver ◽

Increased Risk

AbstractThe hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04–1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09–1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.

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Are Circulating Mg2+ Levels Associated with Glucose Tolerance Profiles and Incident Type 2 Diabetes?

Nutrients ◽

10.3390/nu11102460 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2460 ◽

Cited By ~ 2

Author(s):

Spiga ◽

Mannino ◽

Mancuso ◽

Averta ◽

Paone ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Detrimental Effect ◽

Significant Negative Correlation ◽

Incident Type ◽

Increased Risk ◽

Incident Type 2 Diabetes ◽

The Relationship

Magnesium (Mg2+) is an enzyme co-factor that plays a key role in many biochemical reactions, as well as in glucose metabolism. Clinical evidences have demonstrated that depletion of serum Mg2+ increases exponentially with the duration of type 2 diabetes mellitus (T2DM). Diabetes is associated with low Mg2+, and hypomagnesemia is associated with insulin resistance, inflammation, and increased risk for cardiovascular disease. In subjects at high risk of inflammation and insulin resistance, supplementation of Mg2+ alone ameliorates both phenotypes, slowing the development and progression of hepatic steatosis. We analyze the relationship between serum Mg2+ levels and the onset of T2DM in a large cohort of well-characterized adult white individuals participating in the CATAMERI study, who were reexamined after a mean follow-up of 5.6 ± 0.9 years. In our analysis we acquired a significant negative correlation between Mg2+ levels, fasting glucose, and 2h-post load glucose in subjects who underwent an OGTT. Moreover, Mg2+ levels correlated negatively with fasting insulin levels, and positively with the lipid profile. As for the detrimental effect of lower circulating Mg2+ levels, our data revealed a significant reduction of T2DM risk of about 20% for each 1 mg/dL increase of circulating Mg2+. The present results are consistent with the theory that Mg2+ supplementation could ameliorate insulin sensitivity reducing the risk to develop T2DM.

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Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001948 ◽

2021 ◽

Vol 9 (1) ◽

pp. e001948

Author(s):

Marion Denos ◽

Xiao-Mei Mai ◽

Bjørn Olav Åsvold ◽

Elin Pettersen Sørgjerd ◽

Yue Chen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Family History ◽

Genetic Predisposition ◽

Effect Modification ◽

P Value ◽

Family History Of Diabetes ◽

Increased Risk ◽

History Of

IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.Research design and methodsThis prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).ResultsOver 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).ConclusionSerum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

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Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?

International Journal of Molecular Sciences ◽

10.3390/ijms22126444 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6444

Author(s):

Anna Gabryanczyk ◽

Sylwia Klimczak ◽

Izabela Szymczak-Pajor ◽

Agnieszka Śliwińska

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Vitamin D ◽

Cancer Risk ◽

Vitamin D Deficiency ◽

Cancer Development ◽

Increased Risk

There is mounting evidence that type 2 diabetes mellitus (T2DM) is related with increased risk for the development of cancer. Apart from shared common risk factors typical for both diseases, diabetes driven factors including hyperinsulinemia, insulin resistance, hyperglycemia and low grade chronic inflammation are of great importance. Recently, vitamin D deficiency was reported to be associated with the pathogenesis of numerous diseases, including T2DM and cancer. However, little is known whether vitamin D deficiency may be responsible for elevated cancer risk development in T2DM patients. Therefore, the aim of the current review is to identify the molecular mechanisms by which vitamin D deficiency may contribute to cancer development in T2DM patients. Vitamin D via alleviation of insulin resistance, hyperglycemia, oxidative stress and inflammation reduces diabetes driven cancer risk factors. Moreover, vitamin D strengthens the DNA repair process, and regulates apoptosis and autophagy of cancer cells as well as signaling pathways involved in tumorigenesis i.e., tumor growth factor β (TGFβ), insulin-like growth factor (IGF) and Wnt-β-Cathenin. It should also be underlined that many types of cancer cells present alterations in vitamin D metabolism and action as a result of Vitamin D Receptor (VDR) and CYP27B1 expression dysregulation. Although, numerous studies revealed that adequate vitamin D concentration prevents or delays T2DM and cancer development, little is known how the vitamin affects cancer risk among T2DM patients. There is a pressing need for randomized clinical trials to clarify whether vitamin D deficiency may be a factor responsible for increased risk of cancer in T2DM patients, and whether the use of the vitamin by patients with diabetes and cancer may improve cancer prognosis and metabolic control of diabetes.

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Cardiovascular events in patients with type 2 diabetes

The British Journal of Diabetes ◽

10.1177/1474651402002001s0201 ◽

2002 ◽

Vol 2 (1_suppl) ◽

pp. S4-S8

Author(s):

Erland Erdmann

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Risk Factor ◽

Adverse Effects ◽

Cardiovascular Events ◽

Left Ventricular ◽

Diabetic Patients ◽

Increased Risk

Diabetes is a common risk factor for cardiovascular disease. Coronary heart disease and left ventricular dysfunction are more common in diabetic patients than in non-diabetic patients, and diabetic patients benefit less from revascularisation procedures. This increased risk can only partly be explained by the adverse effects of diabetes on established risk factors; hence, a substantial part of the excess risk must be attributable to direct effects of hyperglycaemia and diabetes. In type 2 diabetes, hyperinsulinaemia, insulin resistance and hyperglycaemia have a number of potential adverse effects, including effects on endothelial function and coagulation. Risk factor modification has been shown to reduce the occurrence of cardiovascular events in patients with diabetes; indeed, diabetic patients appear to benefit more in absolute terms than non-diabetic patients. There is thus a strong case for intensive treatment of risk factors, including insulin resistance and hyperglycaemia, in patients with type 2 diabetes.

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CANCER OF THE ORGANS OF THE REPRODUCTIVE SYSTEM IN WOMEN WITH TYPE 2 DIABETES. EFFECTS OF ANTIDIABETIC THERAPY

Wiadomości Lekarskie ◽

10.36740/wlek202005124 ◽

2020 ◽

Vol 73 (5) ◽

pp. 967-971

Author(s):

Tamara S. Vatseba

Keyword(s):

Type 2 Diabetes ◽

Combination Therapy ◽

Postmenopausal Women ◽

Reproductive System ◽

Uterine Cancer ◽

Antidiabetic Therapy ◽

Increased Risk ◽

Risk Of Cancer ◽

The Impact

The aim: to investigate the prevalence of cancer of the reproductive system in women with type 2 diabetes, and to examine the impact of antidiabetic therapy on cancer risk of this localization. Materials and methods: The study included a retrospective analysis of medical records of women with T2D with first diagnosed cancer during 2012-2016. The bases for the study were specialized medical institutions in Ivano-Frankivsk region. The obtained results were processed using statistical programs “Microsoft Excel” and “Statistika-12”. Results: Breast, uterine, and ovarian cancer were detected in 202 postmenopausal women, 63.92% from the total number of cancer cases in women. An increased risk of breast [OR = 1.24; 95% CI (1.04 – 1.50) P = 0.019] and uterine cancer [OR = 1.32; 95% CI (1.02 – 1.69) P = 0.040] has been identified. Most often, before the detection of cancer, women received combination therapy with sulfonylurea and metformin (83 patients (57.64%)) with BMI 32.64 ± 3.69 kg/m2. The difference between risk of cancer on metformin monotherapy and on sulfonylurea monotherapy [OR = 2.17; 95% CI (0.88 – 5.36) P = 0.141] or on combination therapy [OR = 1.68; 95% CI (0.76 – 3.74) P = 0.276] was not found. Conclusions: Postmenopausal women have an increased risk of breast and uterine cancer and are recommended to be screened for these diseases

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Prevalence of osteoporosis and osteoporotic fractures in postmenopausal women with type 2 diabetes mellitus

Beyond Rheumatology ◽

10.4081/br.2021.71 ◽

2021 ◽

Vol 3 (3) ◽

Author(s):

Lamia Oulkadi ◽

Bouchra Amine ◽

Imane El binoune ◽

Samira Rostom ◽

Rachid Bahiri

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Postmenopausal Women ◽

Mineral Density ◽

Control Subjects ◽

Increased Risk ◽

Significant Difference ◽

Prevalence Of Osteoporosis

Type 2 diabetes mellitus (T2DM) and osteoporosis are chronic diseases with increasing prevalence. The aim of this study was to determine the prevalence of osteoporosis and osteoporotic fracture in women with T2DM and to identify predictive factors of fracture occurrence. The prevalence of osteoporosis and fractures in postmenopausal women with T2DM was 23.1% and 16.9%, respectively. 46.2% of T2DM patients had normal bone mineral density (BMD) (P<0.01) and 58.5% of control subjects had osteopenia (P<0.01). Incidence of fracture in T2DM patients with osteopenia was significantly increased versus control subjects when stratified according the BMD (P=0.009). By stratifying T2DM patients according to fractures, factors that were significantly associated with occurrence included T2DM duration (P=0.038), use of insulin (P=0.017), and lower BMD (P=0.048). Our study suggests that there was a higher prevalence of fracture in T2DM patients compared to control subjects and a significant difference in BMD was found between the groups. We also showed that insulin use, low BMD, and long duration of T2DM are factors associated with an increased risk of bone fracture.

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Myopia and Early Onset Type 2 Diabetes: A Nationwide Cohort Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab669 ◽

2021 ◽

Author(s):

Alon Peled ◽

Itamar Raz ◽

Inbar Zucker ◽

Estela Derazne ◽

Jacob Megreli ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cohort Study ◽

Young Adulthood ◽

Military Service ◽

High Myopia ◽

Continuous Variable ◽

Dependent Manner ◽

Increased Risk

Abstract Objective A correlation between myopia and insulin-resistance has been suggested. We investigated the association between myopia in adolescence and type 2 diabetes (T2D) incidence in young adulthood. Design Population-based, retrospective, cohort study. Methods 1,329,705 adolescents (579,543 women, 43.6%) aged 16-19 years, medically examined before mandatory military service during 1993-2012; and whose data were linked to the Israel National Diabetes Registry. Myopia was defined based on right eye refractive data. Cox proportional models were applied, separately for women and men, to estimate hazard ratios (HRs) for T2D incidence per person-years of follow-up. Results There was an interaction between myopia and sex with T2D (P<0.001). For women, T2D incidence rates (per 100,000 person-years) were 16.6, 19.2, and 25.1 for those without myopia, and with mild-to-moderate and high myopia, respectively. These corresponded to HRs of 1.29 (95%CI 1.14-1.45) and 1.63 (1.21-2.18) for women with mild-to-moderate and high myopia, respectively, compared to those without myopia, after adjustment for age at study entry, birth year, adolescent BMI, cognitive performance, socioeconomic status, and immigration status. Results persisted in extensive sensitivity and subgroup analyses. When managed as a continuous variable, every 1 diopter lower spherical equivalent yielded a 6.5% higher adjusted HR for T2D incidence (P= 0.003). There was no significant association among men. Conclusions For women, myopia in adolescence was associated with a significantly increased risk for incident T2D in young adulthood, in a severity-dependent manner. This finding may support the role of insulin resistance in myopia pathogenesis.

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Glucagon-like peptide-1 (GLP-1) Biological Role in Patients of Type 2 Diabetes and Metabolic Syndrome

The Indian Journal of Nutrition and Dietetics ◽

10.21048/ijnd.2019.56.2.20967 ◽

2019 ◽

Vol 56 (2) ◽

pp. 227

Author(s):

Mohammedziyad Abu Awad

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Glucagon Secretion ◽

Diabetic Patients ◽

Metabolic Disturbances ◽

Cvd Risk ◽

First Line Therapy ◽

Increased Risk ◽

Glucagon Like Peptide 1

<p style="margin: 0in 0in 10pt; text-align: justify; line-height: 200%;">Type2 diabetes is estimated to affect 380 million people worldwide in 2025. Patients of this disease are at increased risk of cardiovascular diseases (CVD).The CVD risk is greater when diabetic patients have metabolic syndrome. Thus, the management of metabolic syndrome and CVD is crucial for diabetic patient’s life progress. GLP-1 has positive biological influences on glucose metabolism control by inhibiting glucagon secretion, enhancing insulin secretion and protecting the effects of cells. GLP-1 was also found to have other positive influences including weight loss, appetite sensation and food intake. These are important factors in metabolic disturbances control and CVD management. The paper reviewed several studies regarding the GLP-1 positive concerns. In conclusion, the paper supports the modern proposal of GLP-1 RAs as a first line therapy in initially diagnosed type 2 diabetes patients.</p>

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Correlation between markers of renal function and sight-threatening diabetic retinopathy in type 2 diabetes: a longitudinal study in an Indian clinic population

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001325 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001325 ◽

Cited By ~ 1

Author(s):

Ramachandran Rajalakshmi ◽

Coimbatore Subramanian Shanthi Rani ◽

Ulagamathesan Venkatesan ◽

Ranjit Unnikrishnan ◽

Ranjit Mohan Anjana ◽

...

Keyword(s):

Type 2 Diabetes ◽

Diabetic Retinopathy ◽

Serum Creatinine ◽

Cox Regression ◽

Tertiary Care ◽

Cox Regression Analysis ◽

Increased Risk ◽

New Onset

IntroductionPrevious epidemiological studies have reported on the prevalence of diabetic kidney disease (DKD) and diabetic retinopathy (DR) from India. The aim of this study is to evaluate the effect of DKD on the development of new-onset DR and sight-threatening diabetic retinopathy (STDR) in Asian Indians with type 2 diabetes (T2D).Research design and methodsThe study was done on anonymized electronic medical record data of people with T2D who had undergone screening for DR and renal work-up as part of routine follow-up at a tertiary care diabetes center in Chennai, South India. The baseline data retrieved included clinical and biochemical parameters including renal profiles (serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria). Grading of DR was performed using the modified Early Treatment Diabetic Retinopathy Study grading system. STDR was defined as the presence of proliferative diabetic retinopathy (PDR) and/or diabetic macular edema. DKD was defined by the presence of albuminuria (≥30 µg/mg) and/or reduction in eGFR (<60 mL/min/1.73 m2). Cox regression analysis was used to evaluate the hazard ratio (HR) for DR and STDR.ResultsData of 19 909 individuals with T2D (mean age 59.6±10.2 years, mean duration of diabetes 11.1±12.1 years, 66.1% male) were analyzed. At baseline, DR was present in 7818 individuals (39.3%), of whom 2249 (11.3%) had STDR. During the mean follow-up period of 3.9±1.9 years, 2140 (17.7%) developed new-onset DR and 980 individuals with non-proliferative DR (NPDR) at baseline progressed to STDR. Higher serum creatinine (HR 1.5, 95% CI 1.3 to 1.7; p<0.0001), eGFR <30 mL/min/1.73 m2 (HR 4.9, 95% CI 2.9 to 8.2; p<0.0001) and presence of macroalbuminuria >300 µg/mg (HR 3.0, 95% CI 2.4 to 3.8; p<0.0001) at baseline were associated with increased risk of progression to STDR.ConclusionsDKD at baseline is a risk factor for progression to STDR. Physicians should promptly refer their patients with DKD to ophthalmologists for timely detection and management of STDR.

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