Physical Exercise and Falling among Older Patients with Diabetes: A Narrative Review

Both diabetes mellitus (DM) and aging have an effect on gait behavior, balance, muscle performance, and other medical complications related to the development of diabetic neuropathy, hypoglycemia, hypotension, cognitive impairment, pain, disturbed proprioceptions, and polypharmacy. The main goal of the present review study was to identify risk variables for hypoglycemia-influenced falling in DM older people, to suggest protective interventions to reduce the occurrence and to explore the effect of physical exercise on falling among elderly individuals with DM. In July 2021, these keywords were used to search Google Scholar, PubMed, Embase: falling in elderly, DM complications, insulin, hypoglycemia, and physical exercise. Because falls are so common during activities, it is critical to figure out what elements influence balance and walking activity. Multi-medications, cognitive dysfunction, dementia, urinary incontinence, depression status, and hypoglycemia are just some of the issues that can affect the elements of controlling balance directly during motion. Others, such as multi-medications, cognitive dysfunction, dementia, urinary incontinence, depression status, and hypoglycemia, can affect balance control indirectly by disrupting posture mobility. Exercise training has been shown to increase body performance and reduce joint discomfort, as well as improve psychological status and quality of life, muscular strength and balance, lower the chance of falling, and improve overall health in the aged and older adults.

The glucagon test in diagnosis of secondary adrenal insufficiency after craniospinal irradiation: the feasibility of application, the features of performing the test, and its diagnostic informativity

BACKGROUND: The glucagon test (GT) is a promising alternative to the insulin hypoglycemia test (IHT) in diagnosis of secondary adrenal insufficiency (SAI). AIM: To study the feasibility of using the GT in patients after craniospinal irradiation and to determine the cut-off value to rule out SAI. METHODS: A total of 28 patients (14 males and 14 females) with the median age of 19 years (17; 23) who had undergone combination treatment (surgery, craniospinal irradiation (35 Gy) with boost to the tumor bed, and polychemotherapy) of extrapituitary brain tumors no later than 2 years before study initiation and 10 healthy volunteers of matching sex and age were examined. All the subjects underwent the GT and IHT with an interval of at least 57 days. The cortisol, ACTH, and glucose levels were measured. RESULTS: Twelve out of 28 patients were diagnosed with SAI according to the IHT results. ROC analysis revealed that cortisol release during the GT 499 nmol/L ruled out SAI [100% sensitivity (Se); 62% specificity (Sp)], while the absence of a rise 340 nmol/l verified SAI (Sp 100%; 55% Se). For GT, the area under a curve (AUC) was 93.6%, which corresponds to a very good diagnostic informativity. In 19 patients, the IHT and GT results were concordant (in ten patients, the release of cortisol occurred above the cut-off value in both tests; no release was detected in nine patients). In nine cases, the results were discordant: the maximum cortisol level detected in the GT was 500 nmol/l, but the IHT results ruled out SAI (the GT yielded a false positive outcome). Contrariwise, in three (10.7%) patients the release of cortisol detected in the GT was adequate, while being insufficient in the IHT test. Adverse events (nausea) were reported during the GT test in 9 (25%) subjects; one patient had hypoglycemia (1.8 mmol/l). CONCLUSION: GT is highly informative and can be used as a first-level stimulation test for ruling out SAI in patients exposed to craniospinal irradiation performed to manage brain tumors. The cortisol level of 500 nmol/L is the best cut-off value for ruling out SAI according to the GT results. The insulin hypoglycemia test is used as the second-level supporting test in patients with positive GT results.

Cortisol and Aldosterone Responses to Hypoglycemia and Na Depletion in Women With Non-Classic 21-Hydroxylase Deficiency

Background Non-classic 21-hydroxylase deficiency is usually diagnosed in post-pubertal women because of androgen excess. Indication of systematic steroid replacement therapy is controversial because the risk of acute adrenal insufficiency is unknown. In order to specify this risk we evaluated the cortisol and aldosterone secretions in response to appropriate pharmacologic challenges. Methods In this prospective case–control non-inferiority study we investigated 20 women with non-classic 21-hydroxylase deficiency carrying biallelic CYP21A2 mutations and with serum 17-hydroxyprogesterone (17OHP) >10 ng/mL after stimulation with Synacthen® (tetracosactrin) and 20 age- and body mass index-matched healthy women with 17OHP after Synacthen® <2 ng/mL. Each participant underwent sequentially an insulin tolerance test to evaluate cortisol secretion and a sodium depletion test, obtained by oral administration of 40 mg of furosemide under low sodium diet (<20 mmol during 24 hours), to evaluate renin and aldosterone secretion. Findings The peak serum cortisol concentration after insulin hypoglycemia was lower in patients than in controls (mean difference –47 ng/mL, 90% CI, –66, P = 0.0026). A peak serum cortisol above a cutoff value of 170 ng/mL was obtained in all controls but only in 55% of patients (P = 0.0039). Twenty-four hours after sodium depletion, blood pressure, plasma sodium, potassium, and serum aldosterone concentrations were comparable between the two groups, but patients had higher stimulated renin concentrations than controls (P = 0.0044). Interpretation Patients with non-classic 21-hydroxylase deficiency frequently display partial cortisol insufficiency and compensated defect in aldosterone secretion. Their clinical management should systematically include assessment of adrenal functions.

Free fatty acid availability is closely related to myocardial lipid storage and cardiac function in hypoglycemia counterregulation

Hypoglycemia, a major side effect of intensive glucose-lowering therapy, was recently linked to increased cardiovascular risk in patients with diabetes. Whether increased circulating free fatty acids (FFA) owing to catecholamine-induced lipolysis affect myocardial energy metabolism and thus link hypoglycemia to cardiac vulnerability is unclear. Therefore, this study investigated the impact of hypoglycemia counterregulation (± inhibition of lipolysis) on myocardial lipid content (MYCL) and left ventricular function in healthy subjects. Nine healthy men were studied in randomized order: 1) insulin/hypoglycemia test (IHT; ins+/aci−), 2) IHT during inhibition of adipose tissue lipolysis by acipimox (ins+/aci+), 3) normoglycemia with acipimox (ins−/aci+), and 4) normoglycemia with placebo (ins−/aci−). MYCL and cardiac function were assessed by employing magnetic resonance spectroscopy/imaging at baseline and at 2 and 6 h. In response to acute hypoglycemia, plasma FFA ( P < 0.0001) and ejection fraction (EF; from 63.2 ± 5.5 to 69.6 ± 6.3%, P = 0.0001) increased significantly and were tightly correlated with each other ( r = 0.68, P = 0.0002); this response was completely blunted by inhibition of adipose tissue lipolysis. In the presence of normoglycemia, inhibition of lipolysis was associated with a drop in EF (from 59.2 ± 5.5 to 53.9 ± 6.9%, P = 0.005) and a significant decrease in plasma FFA, triglycerides, and MYCL (by 48.5%, P = 0.0001). The present data indicate that an intact interorgan cross-talk between adipose tissue and the heart is a prerequisite for catecholamine-mediated myocardial contractility and preservation of myocardial lipid stores in response to acute hypoglycemia.

Hypoglycemia in Type 2 Diabetes—Consequences and Risk Assessment

Although hypoglycemia has traditionally been considered a significant complication of the treatment of type 1 diabetes, the greater incidence of type 2 diabetes compared with type 1, the intensive treatment strategies currently employed, and the longer life expectancy of patients with diabetes, give rise to a large number of type 2 patients at risk for hypoglycemia. This number is likely to rise in an aging population with the increasing use of insulin to treat diabetes. The highest incidence of hypoglycemia is seen in older patients with poor glycemic control and is associated with the use of antidiabetic agents that increase blood insulin concentrations independently of blood glucose concentration (oral antidiabetic drugs or exogenous insulin). Hypoglycemia has a substantial clinical impact in terms of mortality, morbidity, and quality of life. The economic impact of severe hypoglycemic events owing to direct hospital costs and the indirect costs of the inability to work are considerable. Furthermore, both patients’ and physicians’ fear of hypoglycemia reduces adherence to therapeutic regimens and limits the ability of current diabetes medications to achieve the level of glycemic control required to prevent disease progression. Newer therapies and improvements in patient education may help patients achieve improved glucose control by safely reducing glycosylated hemoglobin (HbA1c) with a lower risk of hypoglycemia.