Alissa R. Segal

Frequent hypoglycemia among elderly patients with poor glycemic control.

BACKGROUND Episodes of hypoglycemia are particularly dangerous in the older population. To reduce the risk of hypoglycemia, relaxation of the standard hemoglobin A(1c) (HbA(1c)) goals has been proposed for frail elderly patients. However, the risk of hypoglycemia in this population with higher HbA(1c) levels is unknown. METHODS Patients 69 years or older with HbA(1C) values of 8% or greater were evaluated with blinded continuous glucose monitoring for 3 days. RESULTS Forty adults (mean [SD] age, 75 [5] years; HbA(1C) value, 9.3% [1.3%]; diabetes duration, 22 [14] years; 28 patients [70%] with type 2 diabetes mellitus; and 37 [93%] using insulin) were evaluated. Twenty-six patients (65%) experienced 1 or more episodes of hypoglycemia (glucose level <70 mg/dL). Among these, 12 (46%) experienced a glucose level below 50 mg/dL and 19 (73%), a level below 60 mg/dL. The average number of episodes was 4; average duration, 46 minutes. Eighteen patients (69%) had at least 1 nocturnal episode (10 pm to 6 am). Of the total of 102 hypoglycemic episodes, 95 (93%) were unrecognized by finger-stick glucose measurements performed 4 times a day or by symptoms. CONCLUSIONS Hypoglycemic episodes are common in older adults with poor glycemic control. Raising HbA(1C) goals may not be adequate to prevent hypoglycemia in this population.

Use of concentrated insulin human regular (U-500) for patients with diabetes

PURPOSE The efficacy and safety of and key clinical considerations for using U-500 insulin human regular in the treatment of high-dose insulin-treated patients in a wide variety of settings are examined. SUMMARY U-500 regular insulin has been available in the United States since 1952, but only recently has it become more commonly prescribed for patients requiring large amounts of insulin to improve their blood glucose control. This use coincides with the increasing rates of obesity and type 2 diabetes associated with significant insulin resistance, which can necessitate the need for doses of insulin exceeding 200 units/day. However, many health care professionals are relatively unfamiliar with this concentrated insulin formulation. U-500 regular insulin has a pharmacokinetic and pharmacodynamic profile that differs from U-100 human insulins and analogues. Although no randomized clinical trials using U-500 insulin have been performed, eight case series (involving 160 patients) have been published. Rare or infrequent occurrences of hypoglycemia with U-500 insulin have been reported. Of the medication errors associated with U-500 insulin, administration and dispensing errors occurred most frequently. With the increase in prescribing of U-500 insulin, pharmacists must be aware of the complex issues involved with appropriate prescribing, dispensing, and provision of patient education to maximize patient safety and avoid administration errors and dosing confusion. CONCLUSION U-500 insulin is efficacious and safe for patients with type 2 diabetes who require a high dosage of insulin to control hyperglycemia. However, health care professionals should be well educated and vigilant about patient safety issues regarding the drugs prescription, dosing, and administration.

Dynamical glucometry: Use of multiscale entropy analysis in diabetes

Diabetes mellitus (DM) is one of the worlds most prevalent medical conditions. Contemporary management focuses on lowering mean blood glucose values toward a normal range, but largely ignores the dynamics of glucose fluctuations. We probed analyte time series obtained from continuous glucose monitor (CGM) sensors. We show that the fluctuations in CGM values sampled every 5 min are not uncorrelated noise. Next, using multiscale entropy analysis, we quantified the complexity of the temporal structure of the CGM time series from a group of elderly subjects with type 2 DM and age-matched controls. We further probed the structure of these CGM time series using detrended fluctuation analysis. Our findings indicate that the dynamics of glucose fluctuations from control subjects are more complex than those of subjects with type 2 DM over time scales ranging from about 5 min to 5 h. These findings support consideration of a new framework, dynamical glucometry, to guide mechanistic research and to help assess and compare therapeutic interventions, which should enhance complexity of glucose fluctuations and not just lower mean and variance of blood glucose levels.

Assessment of barriers to improve diabetes management in older adults: a randomized controlled study.

OBJECTIVE To evaluate whether assessment of barriers to self-care and strategies to cope with these barriers in older adults with diabetes is superior to usual care with attention control. The American Diabetes Association guidelines recommend the assessment of age-specific barriers. However, the effect of such strategy on outcomes is unknown. RESEARCH DESIGN AND METHODS We randomized 100 subjects aged ≥69 years with poorly controlled diabetes (A1C >8%) in two groups. A geriatric diabetes team assessed barriers and developed strategies to help patients cope with barriers for an intervention group. The control group received equal amounts of attention time. The active intervention was performed for the first 6 months, followed by a “no-contact” period. Outcome measures included A1C, Tinetti test, 6-min walk test (6MWT), self-care frequency, and diabetes-related distress. RESULTS We assessed 100 patients (age 75 ± 5 years, duration 21 ± 13 years, 68% type 2 diabetes, 89% on insulin) over 12 months. After the active period, A1C decreased by −0.45% in the intervention group vs. −0.31% in the control group. At 12 months, A1C decreased further in the intervention group by −0.21% vs. 0% in control group (linear mixed-model, P < 0.03). The intervention group showed additional benefits in scores on measures of self-care (Self-Care Inventory-R), gait and balance (Tinetti), and endurance (6MWT) compared with the control group. Diabetes-related distress improved in both groups. CONCLUSIONS Only attention between clinic visits lowers diabetes-related distress in older adults. However, communication with an educator cognizant of patients’ barriers improves glycemic control and self-care frequency, maintains functionality, and lowers distress in this population.

Simplification of Insulin Regimen in Older Adults and Risk of Hypoglycemia.

If 50% of the fasting finger-stick readings/wk are higher than goal: Increase glargine dose by 2 unitsb If more than 2 finger-stick readings/wk are <80 mg/dL: Decrease glargine dose by 2 unitsb If meal-time insulin is <10 U/dose: Discontinue and add noninsulin agent If meal-time insulin >10 U/dose: Decrease by 50% and add noninsulin agent Continue to titrate dose of meal-time insulin down as noninsulin agent is increased

Shortfalls of the use of HbA1C-derived eAG in older adults with diabetes

AIMS The hemoglobin HbA1C (HbA1C) value, translated into estimated average glucose concentration (eAG), is commonly used to assess glycaemic control and manage treatment regimens in people with diabetes. However, the relationships among HbA1C-derived eAG, and mean glucose concentration derived from continuous glucose monitoring (CGM) in different populations have not been well studied. We examined this relationship in older people with diabetes and compared the results to those currently used in clinical practice. METHODS Data from three studies evaluating CGM in older adults (≥70 years of age), with stable glycaemic control were analyzed retrospectively. Mean glucose and mean amplitude of glucose excursion (MAGE) were calculated from CGM data and correlated with HbA1C and HbA1C-derived eAG using the ADAG study formula. RESULTS HbA1C and CGM data were analyzed from 90 patients with mean age 76±5 years, HbA1C 7.9±1.2% (63±13 mmol/mol) and 77% with Type 2 diabetes. The HbA1C and HbA1C-derived eAG correlated significantly with CGM-measured mean glucose (r(2)=0.30, p<0.0001) and MAGE (r(2)=0.16, p=0.00013) in this population and all its subgroups, but the slopes of the relationship between HbA1C and eAG or CGM-measured mean glucose were significantly different. CONCLUSIONS HbA1C-derived eAG values may not accurately reflect CGM-measured mean glucose or MAGE in older adults with diabetes. Wide glucose excursions should be considered and HbA1C should be interpreted cautiously when making treatment changes based on HbA1C.

Are You Ready for More Insulin Concentrations

Practitioners need to prepare for a rapid expansion of new concentrated insulins. For many years, the treatment regimens for patients have been limited to 2 concentrations (100 units/mL and 500 units/mL), which pose challenges to both patients and providers. As the new concentrated insulins are at various stages of development, this manuscript reviews the available information on the new concentrated products. This information was obtained from publications, poster presentations, abstracts, and the manufacturers for the products in earlier stages of development. To have a basis for comparison, it is important to understand the activity profile and the challenges with use of the currently available concentrated insulin, regular insulin 500 units/mL (U500R). We also examine how the newer products may assist clinicians and patients with the difficulties faced with the use of U500R.

Treatment of Type 2 Diabetes in the Elderly

As the number of older adults increases in the United States and worldwide, management of patients with multiple coexisting chronic diseases has become a critical component in health care. Management of diabetes is particularly challenging in this population due to significant risks of microvascular and macrovascular diseases on the one hand, and complications of the treatment strategies (e.g., hypoglycemia) with intensive control on the other hand. To provide a balanced approach to diabetes in the elderly, a comprehensive and holistic strategy, with consideration of overall health, functional status, psychosocial environment, financial resources and, finally but most importantly, quality of life is needed. Understanding the unique challenges faced by older adults with diabetes and issues pertaining to antidiabetes medications with aging is an important first step in the direction of better and tailored care of this burgeoning population.

Liberating A1C goals in older adults may not protect against the risk of hypoglycemia

AIMS Hemoglobin A1C is universally used as a marker for glycemic control and to establish glycemic goals in patients with diabetes. In the older population, experts recommend liberating A1C goals to decrease the risk of hypoglycemia. However, its not clear which A1C level is optimal for this purpose. This studys aim was to understand the relationship between A1C levels and risk of hypoglycemia. METHODS In a prospective study, we performed continuous glucose monitoring (CGM) on older adults on insulin. Hypoglycemia duration and A1C were measured at baseline while patients were on multiple insulin injections, and again after de-intensification to once-a-day basal insulin with non-insulin agents. RESULTS We assessed 65 patients; mean age76±6years with on average 3.7±1.3 insulin injections/day. At baseline, 26% of the patients had A1C<7% (53mmol/mol), 42% between 7.1% and 8% (54-64mmol/mol), 21% between 8.1% and 9% (65-75mmol/mol), and 11% >9% (76mmol/mol). The duration of hypoglycemia (<70mg/dl, <60mg/dl, <50mg/dl) was not different between the A1c groups, regardless of treatment intensity (multiple insulin injections or once-a-day-basal insulin with non-insulin agents). CONCLUSIONS A1C levels are not associated with hypoglycemia risk in older population with type-2 diabetes on insulin therapy. Higher A1C goals do not protect against hypoglycemia.

Renal Function Alters Antihypertensive Regimens in Type 2 Diabetic Patients.

To determine the prevalence of multidrug antihypertensive therapy (MDAT), records were evaluated for patients with both type 2 diabetes and hypertension during a 5‐year period at Joslin Diabetes Center. Hypertension control was defined as requiring multiple drugs if three or more antihypertensive drugs were used, one of which must be a diuretic (unless patient is receiving dialysis), or use of four or more antihypertensive drugs, one of which a diuretic (unless patient is receiving dialysis) was established. The objective was to determine the prevalence of multidrug requirement for hypertensive therapy in relationship to four levels of renal function estimated by the Modification of Diet in Renal Disease formula for glomerular filtration rate (GFR). Among 10,151 patients, mean estimated GFR was 80 mL/min. Using standard (ASN) classification for renal function, we noted the following breakdown of MDAT use: