The Cardiometabolic Syndrome and Risk of Mortality From Cardiovascular Diseases and All Causes Among African Americans and White Americans

Longjian Liu¹, Zuolu Liu², Marshal Ma³, Fuzhong Xue⁴ and Eliot Sorel⁵

Affiliations: ¹Department of Epidemiology and Biostatistics, Drexel University School of Public Health, Philadelphia, Pennsylvania, USA; ²Temple University School of Medicine, Philadelphia, Pennsylvania, USA; ³Bureau of Epidemiology, Pennsylvania Department of Health, Harrisburg, Pennsylvania, USA; ⁴Department of Epidemiology and Biostatistics, Shandong University School of Public Health, Jinan, Shandong Province, China and ⁵The George Washington University School of Medicine and Health Sciences, and School of Public Health and Health Services, Washington, DC, USA

ABSTRACT

AIM

Studies using representative national data to prospectively examine associations between cardiometabolic syndrome (CMS) and mortality risk from cardiovascular diseases (CVD) and all causes by race/ethnicity are scarce. We tested the association using the Third National Health and Nutrition Examination Survey Linked Mortality File (1988–2006).

METHODS

CMS is defined using criteria from the National Cholesterol Education Program, with minor modifications based on criteria from the American Heart Association. Associations between CMS and mortality risk in those aged ≥35 years old were examined prospectively using Cox proportional hazard regression models.

RESULTS

The results indicate that almost one third of Americans aged ≥35 years have CMS. There were significant differences in prevalence of CMS components between African American and White participants. Multivariable-adjusted hazard ratios (95% CI) of CMS for CVD and all cause mortality were 1.34 (1.10–1.64), and 1.36 (1.21–1.54) in African Americans, and 1.31 (1.17–1.46) and 1.22 (1.13–1.31) in Whites. The CMS-mortality associations were greatly reduced after adjustment for inflammatory biomarkers.

CONCLUSIONS

CMS significantly predicts CVD and all cause mortality. The high prevalence of CMS poses a serious health problem in the United States. Specific attention should be paid to the significant race/ethnicity differences in CMS components rates and the effects of inflammatory disorders on CMS-mortality association when designing programs for prevention and treatment of the syndrome.

Keywords: cardiometabolic syndrome, CVD, all cause mortality

Correspondence: Longjian Liu, MD, PhD, MSc, FAHA, Associate Professor, Department of Epidemiology and Biostatistics, Drexel University School of Public Health, Philadelphia, PA 19102, USA. Tel: +215 762 1370; Fax: 215 762 1174; e-mail: Longjian.Liu@drexel.edu

Thyroid Autoimmunity in Subjects with Type 1 Diabetes Mellitus: An Analysis of Prevalence Within a Defined Geographical Area in Sicily, Italy

Domenico Greco, Maria Pisciotta, Francesco Gambina and Filippo Maggio

Affiliation: Division of Diabetology, ‘‘Paolo Borsellino’’ Hospital, Marsala, Italy

ABSTRACT

BACKGROUND

Thyroid autoimmunity is the most prevalent immunological process affecting subjects with type 1 diabetes. Aim of this work was to investigate thyroid autoimmunity in a large cohort of type 1 diabetic subjects all coming from a defined geographical area.

METHODS

Data were analyzed from 374 patients who were treated in a diabetes center in western Sicily (Italy), over a 2.5 year period. TPO-Ab, TSH, FT3, and FT4 were measured and documented at least once in all these patients.

RESULTS

During the period of the survey TPO-Ab were present in 108 patients, resulting in an overall prevalence of 28.8%; the female-to-male ratio was > 2:1. TPO-Ab+ patients showed an age at diabetes onset significantly higher. The thyroid status of most of these patients was euthyroidism (54 subjects) but overt hypothyroidism (38 subjects), subclinical hypothyroidism (13 subjects), and hyperthyroidism (three subjects) were also present. Subjects with overt hypothyroidism were significantly older than others and showed an age at diabetes diagnosis higher than euthyroid subjects.

CONCLUSIONS

Our data confirm the strong association between thyroid autoimmunity and type 1 diabetes in a Sicilian population. Therefore, in type 1 diabetic patients, an active search for the presence of autoimmune thyroiditis is warranted, particularly in female subjects.

Keywords: type 1 diabetes mellitus, autoimmune thyroid disease, thyroid autoimmunity

Correspondence: Dr. Domenico Greco, Via Cosenza, 155, 91016 Erice (TP), Italy. Tel:
39-0923753175, Fax:
39-0923753174; e-mail: drgreco@alice.it

Dyslipidemia: A Review of Pathophysiology and Lipoprotein Disorders

Stanley K. Zimmerman and James L. Vacek

Affiliation: University of Kansas Hospital and Medical Center, Kansas City, KS, USA

ABSTRACT

Coronary heart disease affects millions of patients around the world, and its prevalence makes understanding the variety of risk factors that contribute to coronary artery disease (CAD) paramount for any clinician. One important risk factor that has been identified is dyslipidemia and the spectrum of lipid disorders that this entails. The relationship between dyslipidemia and CAD is well established, and clinically it is important to understand the basic pathophysiology for disease prevention and treatment. Fats are essential to life and are metabolized and circulated in the body through the lipid transport system. Their storage, regulation, and processing are maintained in a fine balance, but with simple alterations can lead to profound consequences including heart attack, stroke, and peripheral vascular disease. An understanding of basic pathophysiology of lipids, their role in the body, and how disruption in their metabolism manifests into systemic disease is a vital part of caring for the ever increasing number of patients with dyslipidemia. Therapeutic approaches to clinical dyslipidemias are described in a prior review on the topic previously published in the Journal of Clinical Metabolism & Diabetes (April 2011 issue) as a companion to the present article.

Keywords: dyslipidemia, coronary heart disease, lipid transport system, lipoproteins, coronary artery disease, lipoprotein disorders

Correspondence: James Vacek, Mid America Cardiology, University of Kansas Hospital and Medical Center, 39th and Rainbow Blvd Kansas City, KS 66061, USA. Tel: +
1 913 5889600; e-mail: jlvacek@mac.md

Inhibition of Renal Glucose Reabsorption as a Novel Strategy for Treatment of Diabetes

Gian Pio Sorice^1,2, Giovanna Muscogiuri^1,2, Teresa Mezza^1,2, Annamaria Prioletta^1,2 Andrea Giaccari^1,2

Affiliations: 1Division of Endocrinology and Metabolic Diseases, Universita` Cattolica, Rome, Italy and 2Don Gnocchi Foundation, Milan, Italy

ABSTRACT

Even though the kidney has been considered a victim of hyperglycemia rather than a target for therapeutic intervention, this organ is principally involved in the regulation of glucose homeostasis through gluconeogenesis and, above all, reabsorption of glucose from the glomerular filtrate. In presence of euglycemia, all the daily filtered glucose (180 g) is reabsorbed by Sodium-GLucose co-Transporters type 2 (SGLT-2), expressed in the brush-border membrane of the proximal renal tubules. These transporters mediate the majority of renal glucose reabsorption from the tubular fluid; when plasma glucose concentration exceeds the potential maximal activity of these transporters, glucose appears in the urine. The SGLT-2 inhibitors reduce SGLT-2 activity and block glucose reabsorption, thus glucose is massively lost with urines and plasma glucose lowers. Since antidiabetic therapeutic weapons presently available do not guarantee a longstanding normoglycemic profile and a combination of different drugs is routinely required to maintain glycemia under acceptable levels, competitive inhibition of SGLT-2 may become a unique mechanism to potentially lower the blood glucose levels in patients with diabetes, avoiding the risk of hypoglycemia and preventing the deleterious effect of hyperglycemia (glucose toxicity and glycemic variability). This review summarizes the functions and the physiology of renal glucose transporters and lastly describes the clinical pharmacology and safety of the SGLT-2 inhibitors, outlining that SGLT-2 inhibitors may represent a novel and safe treatment option for diabetes.

Keywords: Type 2 diabetes mellitus treatment, renal glucose reabsorption, glucosuria, glucose toxicity, glucotoxicity, glucose variability,SGLT-2, SGLT-2 inhibitor, sergliflozin, remogliflozin, dapagliflozin, canagliflozin

Correspondence: Andrea Giaccari, Endocrinology, Policlinico Gemelli, Largo A. Gemelli 8, 00168 Rome, Italy. e-mail: giaccari@rm.unicatt.it

Current Questions on Proteinuria and Albuminuria

Anna V Oláh^1*, Bertalan Fodor² and János Mátyus³

Affiliations: ¹Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; ²Faculty of Health, University of Miskolc, Miskolc, Hungary; ³Department of Medicine, University of Miskolc, Miskolc, Hungary

ABSTRACT

According to current clinical trials, albumin excretion not only indicates kidney damage but it is also a risk factor for the progression of kidney disease and future cardiovascular events. While proteinuria is considered as a marker of kidney function, microalbuminuria, first of all, indicates cardiovascular risk. Sensitivity of the laboratory tests is method dependent, some of the previously used tests do not meet the clinical requirements, and the error of urine collection makes the results misleading. To avoid these preanalytical problems, recent guidelines suggest the calculation of albumin and creatinine ratio (ACR) and protein and creatinine ratio (PCR) from the values measured from the first morning urine, as these ratios correlate well with the corresponding results of properly collected 24-hour urine. For the clinical diagnosis of albuminuria, the sensitive immunoturbidimetric assays are recommended. Because of poor sensitivity, urinary albumin dipsticks are not recommended for the measurement of albuminuria. For the diagnosis of proteinuria, wide-range urinary protein reagents are available with high sensitivity. The traceability of calibrator to a reference material is a critical requirement. For these reasons, proteinuria and albuminuria of a patient should be monitored in the same laboratory, using a fixed method and cut-off value. Protein, albumin, and creatinine should be measured from the same urine sample, practically using the same analyzer. The ACR values should be reported together with gender-dependent reference ranges. As the PCR range is wider, the same cut-off value can be used for men and women. We discuss the interpretation and diagnostic algorithm of proteinuria and albuminuria.

Keywords: ACR, albuminuria, cardiovascular disease, chronic kidney disease, proteinuria, protein/creatinine

Correspondence: Anna V Oláh, Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, Debrecen, POB 70, H-4032, Hungary; e-mail: olaha@dote.hu

Proteinuria in Pregnancy

Sarah Ruth Hart¹, Khaled M K Ismail^1,2

Affiliations: ¹Institute of Science and Technology in Medicine, Keele University, School of Medicine, Keele, ST5 5BG, England, ²Professor of Obstetrics & Gynaecology, School of Clinical & Experimental Medicine, College of Medical & Dental Sciences, University of Birmingham, Birmingham B15 2 TT, England

ABSTRACT

Checking for proteinuria is routinely performed during every antenatal appointment both in primary and secondary as a screening test for pre-eclampsia. Even in the absence of raised blood pressure, the presence of significant proteinuria during the antenatal period is taken seriously, because proteinuria is perceived to be a diagnostic marker for maternal and fetal complications. The appearance of proteinuria prior to hypertension onset and the diagnosis of pre-eclampsia is well documented in the literature; hence, the presence of proteinuria per se warrants medical referral, investigations, and increased antenatal monitoring frequency. In this review, the authors examine the pathology relating to proteinuria, methods used in its biochemical assessment, and the current evidence relating to the diagnostic and prognostic accuracy of this test in relation to pre-eclampsia.

Keywords: proteinuria, toxaemia, pregnancy, kidney, hypertension

Correspondence: Dr Khaled M K Ismail MSc, MD, PhD, FRCOG, Professor of Obstetrics & Gynaecology, School of Clinical & Experimental Medicine, College of Medical & Dental Sciences, University of Birmingham, Birmingham B15 2 TT, England. Tel: +44 (0)1782 672377, Fax: +44 (0)1782 672137; e-mail: k.m.k.ismail@obst.keele.ac.uk

The Role of IRS-1 Serine Phosphorylation in Insulin Resistance induced by Stress and Nutrient Signaling

Wenshuo Zhang and Xiao Jian Sun

Affiliation: Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Chicago, Chicago, IL, USA

ABSTRACT

Obesity and overeating are linked to insulin resistance and type 2 diabetes, and caloric restriction is known to alleviate insulin resistance and improve the outcome of diabetes. Insulin resistance is characterized by attenuation in the efficacy of insulin to promote nutrient clearance and partitioning, and is worsened by elevated levels of inflammatory hormones, hyperglycemia, hyperinsulinemia, and hyperaminoacidemia, all of which may occur secondary to chronic nutrient excess. These agents induce a resistant state through stress and nutrient signaling pathways that upregulate the activity of serine kinases, which in turn negatively feed back on insulin signaling molecules. The insulin receptor substrate (IRS) proteins are key upstream insulin signaling mediators which, when serine phosphorylated, fail to effectively transmit the insulin signal downstream, resulting in insulin resistance. In this review, we focus on the role of overnutrition-induced IRS-1 serine phosphorylation on specific sites within the IRS-1 molecule that have been demonstrated to be critical regulatory targets with respect to insulin signaling. The means by which upregulation of stress- and nutrient-associated kinases, specifically Erk and mTOR/p70S6K, lead to serine phosphorylation of IRS-1 and insulin resistance are discussed.

Keywords: insulin resistance, obesity, insulin receptor substrate (IRS), MAPK, mTOR, p70S6K

Correspondence: Xiao Jian Sun, Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Chicago, Chicago, IL 60540, USA. e-mail: xsun@medicine.bsd.uchicago.edu

Oedema Associated With Improved Glycaemic Control in a 15-Year-Old Nigerian Girl With Type 1 Diabetes Mellitus Complicated by Ketoacidosis

Alphonsus N. Onyiriuka and Frances A. Ehirim

Affiliation: Department of Child Health, University of Benin Teaching Hospital, Benin, Nigeria

ABSTRACT

In this article, we reported a recent case of a 15-year-old grossly underweight ( weighed 29 kg) Nigerian girl diagnosed of type 1 diabetes mellitus 4 years ago and who defaulted from follow-up but presented with diabetic ketoacidosis. Her glycaemic control was poor because of poor compliance. Following treatment with insulin infusion, she developed facial swelling on the fifth day of admission, followed by pitting ankle and pretibial oedema two days later. The natural history of insulin-induced oedema was observed in this patient because the oedema resolved 7 days later without any specific therapy, such as administration of diuretics. The aim of this article was to review existing medical literature on the subject of insulin-induced oedema and raise the awareness of clinicians of the occurrence of oedema as an uncommon complication of insulin therapy. In conclusion, insulin-induced oedema should be considered in the differential diagnosis of oedema in children and adolescents with type 1 diabetes mellitus.

Keywords: Insulin therapy, oedema, childhood diabetes mellitus, Nigeria

Correspondence: Dr A.N. Onyiriuka, Department of Child Health, University of Benin Teaching Hospital, PMB 1111, Benin CITY, Nigeria. Tel: +234 803 252 9437; e-mail: alpndiony@yahoo.com