Researchers at the Hiroshima University have investigated the interrelationships between various stages of impaired glucose metabolism, hypertension and insulin resistance, an association that is not fully understood. Their findings reveal that although hypertension increases as impaired glucose metabolism gets worse, hyperinsulinemia and hyperglycemia also play a significant role in the prevalence of hypertension when impaired insulin metabolism is in its early stages.
Moreover, at the onset, or in the early stages of impaired glucose metabolism, plasma glucose levels may have a crucial role in maintaining blood pressure, as reported in the Journal of the American Heart Association (AHA).
Associations between Hyperglycemia, Insulin Resistance, Hyperinsulinemia, Hypertension and Diabetes Mellitus
As established by previous studies, hypertension and diabetes mellitus (DM) often exist together. Both these conditions are potentially connected through insulin resistance, which is defined as a reduced response to insulin stimulation of target tissues. Insulin resistance is characterized via hyperglycemia (high levels of sugar/glucose in blood) and compensatory hyperinsulinemia (excess levels of insulin circulating in blood relative to the level of glucose). While hyperglycemia causes fluid to move from intracellular to extracellular spaces, causing plasma volume expansion and subsequent increase in blood pressure, hyperinsulinemia increases the rate of sodium absorption from renal tubules, renin excretion, and sympathetic nervous activity, all of which directly lead to blood pressure elevation.
In most cases, both hyperglycemia and insulin resistance lead to vascular damage via many intermediate pathways, including oxidative stress (imbalance between free radicals and antioxidants in the body) and inflammation which ultimately causes increased arterial stiffness and hypertension. However, the mechanisms through which hypertension develops in the different types of pre-diabetes is not well understood. For example, impaired fasting glucose (IFG), a form of pre-diabetes, is categorized by a notable increase in hepatic insulin resistance and elevated fasting blood glucose levels. Similarly, impaired glucose tolerance (IGT), another type of pre-diabetes, leads to a marked rise in insulin resistance of skeletal muscles and elevated postprandial (after a meal) glucose levels. These specific pathways found in the pathophysiology of pre-diabetes might have potentially diverse impacts on blood pressure and resistant vessels.
Data Collection and Findings
Data was collected from Hiroshima GMCVD (Hiroshima Study on Glucose Metabolism and Cardiovascular Diseases) – a cross-sectional and longitudinal study examining the interrelationships between impaired glucose metabolism, blood pressure and cardiovascular outcomes. Study participants were enrolled from examinees that completed a general health examination provided as part of a government service for atomic bomb survivors in Hiroshima City at the Health Management and Promotion Center of the Hiroshima Atomic Bomb Casualty Council (January 1982 to November 2017). During the checkup, participants were questioned about their usual medications and medical history, with special focus on hypertension, cardiovascular disease and dyslipidemia, along with drinking or smoking habits. Inclusion criteria were considered as a) no history of anti-diabetic medication, b) doubtful impaired glucose metabolism based on screenings of fasting plasma glucose and postprandial plasma glucose, and c) agreement to take the 75g oral glucose tolerance tests (OGTTs).
Ultimately, the impact of insulin resistance, serum immuno-reactive insulin levels and plasma glucose on hypertension was evaluated in 19,166 participants with varying stages of impaired glucose metabolism, as determined by the 75g oral glucose tolerance tests (OGTTs). The percentage of hypertension was found to increase from 36.3% among participants with normal fasting glucose/normal glucose tolerance, to 50.1% in participants with isolated impaired fasting glucose, 50.8% in participants with isolated impaired glucose tolerance, 58.3% in those with impaired fasting glucose and impaired glucose tolerance, and 63.8% in participants with diabetes mellitus. Homeostasis model assessment (method for assessing β-cell function and insulin resistance from fasting glucose and insulin concentrations) of insulin resistance was associated with hypertension irrespective of impaired glucose metabolism. Moreover, fasting plasma glucose and levels of serum immuno-reactive insulin were associated with hypertension in normal fasting glucose and isolated impaired fasting glucose; however, this relationship was reduced in other types of diabetes mellitus and pre-diabetes.
Results of the study clearly demonstrate a correlation between the different stages of impaired glucose metabolism, namely pre-diabetes and diabetes mellitus, and the prevalence of hypertension. Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) both have additional effects on blood pressure leading to a higher prevalence of hypertension during the advanced stages of impaired glucose metabolism. In comparison, hyperglycemia and hyperinsulinemia were found to significantly contribute towards hypertension only in the early stages of impaired glucose metabolism.
These observations support the assumptions that both hyperglycemia and hyperinsulinemia may be important factors in the initiation of hypertension in the early stages of insulin resistance, hence being a significant determinant of prognosis in patients with impaired glucose metabolism. That’s why researchers have focused on the importance of investigating what the effect of timely interventions to control impaired glucose metabolism will be on blood pressure, since this might play a vital role in reducing cardiovascular events.