Diabetes and Hypertension: Is There a Common Metabolic Pathway?

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Abstract

Diabetes and hypertension frequently occur together. There is substantial overlap between diabetes and hypertension in etiology and disease mechanisms. Obesity, inflammation, oxidative stress, and insulin resistance are thought to be the common pathways. Recent advances in the understanding of these pathways have provided new insights and perspectives. Physical activity plays an important protective role in the two diseases. Knowing the common causes and disease mechanisms allows a more effective and proactive approach in their prevention and treatment.

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Most cited references 88

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Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells.

K K Griendling, C A Minieri, J D Ollerenshaw … (1994)

The signaling pathways involved in the long-term metabolic effects of angiotensin II (Ang II) in vascular smooth muscle cells are incompletely understood but include the generation of molecules likely to affect oxidase activity. We examined the ability of Ang II to stimulate superoxide anion formation and investigated the identity of the oxidases responsible for its production. Treatment of vascular smooth muscle cells with Ang II for 4 to 6 hours caused a 2.7 +/- 0.4-fold increase in intracellular superoxide anion formation as detected by lucigenin assay. This superoxide appeared to result from activation of both the NADPH and NADH oxidases. NADPH oxidase activity increased from 3.23 +/- 0.61 to 11.80 +/- 1.72 nmol O2-/min per milligram protein after 4 hours of Ang II, whereas NADH oxidase activity increased from 16.76 +/- 2.13 to 45.00 +/- 4.57 nmol O2-/min per milligram protein. The NADPH oxidase activity was stimulated by exogenous phosphatidic and arachidonic acids and was partially inhibited by the specific inhibitor diphenylene iodinium. NADH oxidase activity was increased by arachidonic and linoleic acids, was insensitive to exogenous phosphatidic acid, and was inhibited by high concentrations of quinacrine. Both of these oxidases appear to reside in the plasma membrane, on the basis of migration of the activity after cellular fractionation and their apparent insensitivity to the mitochondrial poison KCN. These observations suggest that Ang II specifically activates enzyme systems that promote superoxide generation and raise the possibility that these pathways function as second messengers for long-term responses, such as hypertrophy or hyperplasia.

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Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study.

Juan Lin, Chien-An Liu, J. Xiao … (1997)

Individuals with impaired glucose tolerance (IGT) have a high risk of developing NIDDM. The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM, i.e., reduce the incidence of NIDDM, and thereby reduce the overall incidence of diabetic complications, such as cardiovascular, renal, and retinal disease, and the excess mortality attributable to these complications. In 1986, 110,660 men and women from 33 health care clinics in the city of Da Qing, China, were screened for IGT and NIDDM. Of these individuals, 577 were classified (using World Health Organization criteria) as having IGT. Subjects were randomized by clinic into a clinical trial, either to a control group or to one of three active treatment groups: diet only, exercise only, or diet plus exercise. Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM. Cox's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment. The cumulative incidence of diabetes at 6 years was 67.7% (95% CI, 59.8-75.2) in the control group compared with 43.8% (95% CI, 35.5-52.3) in the diet group, 41.1% (95% CI, 33.4-49.4) in the exercise group, and 46.0% (95% CI, 37.3-54.7) in the diet-plus-exercise group (P or = 25 kg/m2). In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose, the diet, exercise, and diet-plus-exercise interventions were associated with 31% (P < 0.03), 46% (P < 0.0005), and 42% (P < 0.005) reductions in risk of developing diabetes, respectively. Diet and/or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT.

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Genetic and environmental factors in relative body weight and human adiposity.

H Maes, M. C. Neale, L J Eaves (1997)

We review the literature on the familial resemblance of body mass index (BMI) and other adiposity measures and find strikingly convergent results for a variety of relationships. Results from twin studies suggest that genetic factors explain 50 to 90% of the variance in BMI. Family studies generally report estimates of parent-offspring and sibling correlations in agreement with heritabilities of 20 to 80%. Data from adoption studies are consistent with genetic factors accounting for 20 to 60% of the variation in BMI. Based on data from more than 25,000 twin pairs and 50,000 biological and adoptive family members, the weighted mean correlations are .74 for MZ twins, .32 for DZ twins, .25 for siblings, .19 for parent-offspring pairs, .06 for adoptive relatives, and .12 for spouses. Advantages and disadvantages of twin, family, and adoption studies are reviewed. Data from the Virginia 30,000, including twins and their parents, siblings, spouses, and children, were analyzed using a structural equation model (Stealth) which estimates additive and dominance genetic variance, cultural transmission, assortative mating, nonparental shared environment, and special twin and MZ twin environmental variance. Genetic factors explained 67% of the variance in males and females, of which half is due to dominance. A small proportion of the genetic variance was attributed to the consequences of assortative mating. The remainder of the variance is accounted for by unique environmental factors, of which 7% is correlated across twins. No evidence was found for a special MZ twin environment, thereby supporting the equal environment assumption. These results are consistent with other studies in suggesting that genetic factors play a significant role in the causes of individual differences in relative body weight and human adiposity.

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Author and article information

Contributors

: +852-22554347 , +852-28186474 , mycheung@hku.hk

: dcli@hku.hk

Journal

Journal ID (nlm-ta): Curr Atheroscler Rep

Journal ID (iso-abbrev): Curr Atheroscler Rep

Title: Current Atherosclerosis Reports

Publisher: Current Science Inc. (New York )

ISSN (Print): 1523-3804

ISSN (Electronic): 1534-6242

Publication date (Electronic): 27 January 2012

Publication date PMC-release: 27 January 2012

Publication date (Print): April 2012

Volume: 14

Issue: 2

Pages: 160-166

Affiliations

[1 ]Department of Medicine, University of Hong Kong, Pokfulam, Hong Kong

[2 ]Department of Medicine, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China

Article

Publisher ID: 227

DOI: 10.1007/s11883-012-0227-2

PMC ID: 3314178

PubMed ID: 22281657

SO-VID: a9a385f2-de93-4957-9dae-b8578d9fd2f4

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ScienceOpen disciplines: Immunology

Keywords: metabolic pathway,hypertension,obesity,insulin resistance,diabetes,metabolic syndrome

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ScienceOpen disciplines: Immunology

Keywords: metabolic pathway, hypertension, obesity, insulin resistance, diabetes, metabolic syndrome

Diabetes and Hypertension: Is There a Common Metabolic Pathway?

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Most cited references 88

Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells.

Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study.

Genetic and environmental factors in relative body weight and human adiposity.

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