Left ventricular metabolism, function, and sympathetic innervation in men and women with type 1 diabetes.

BACKGROUND: In type I diabetes (T1DM), alterations in LV function may occur due to changes in innervation, metabolism, and efficiency. OBJECTIVES: We evaluated the association between sympathetic nerve function, oxidative metabolism, resting blood flow, LV efficiency and function in healthy diabetics, and assessed gender differences. METHODS: Cross-sectional study of 45 subjects with T1DM, 60% females, age 34 ± 13 years, and 10 age-matched controls. Positron emission tomography (PET) imaging with [(11)C]acetate and [(11)C]meta-hydroxyephedrine was performed, in addition to cardiac magnetic resonance imaging. RESULTS: There were no significant differences in LV function, innervation, or oxidative metabolism between T1DM and controls. Cardiac oxidative metabolism was positively associated with higher levels of sympathetic activation, particularly in women. Diabetic women had significantly lower efficiency compared with diabetic men. Resting flow was significantly higher in diabetic women compared with diabetic men, and tended to be higher in female controls as well. CONCLUSIONS: Measures of myocardial function, metabolism, blood flow, and sympathetic activation were preserved in young, otherwise healthy, T1DM patients. However, T1DM women presented with greater myocardial oxidative metabolism requirements than men. Ongoing studies are evaluating changes over time.

The care continuum in acromegaly: how patients, nurses, and physicians can collaborate for successful treatment experiences.

Patients with acromegaly (a condition of chronic growth hormone hypersecretion by a pituitary adenoma) often require pharmacological treatment. Somatostatin analogs (SSAs) such as pasireotide, lanreotide, and octreotide are frequently used as first-line medical therapy. As SSAs are delivered by regular subcutaneous or intramuscular injections, they can result in injection-related pain or anxiety and can be challenging to fit into patients' lifestyles. When combined with the prolonged, debilitating psychological complications associated with acromegaly, these administration challenges can negatively impact compliance, adherence, and quality of life. Proactively managing patients' expectations and providing appropriate, timely guidance are crucial for maximizing adherence, and ultimately, optimizing the treatment experience. As part of ongoing clinical research since 1997, our team at the University of Michigan has used SSAs to treat 30 patients with acromegaly. Based on our clinical experiences with multiple SSA administration regimens (long-acting intramuscular, long-acting deep subcutaneous, and twice-daily subcutaneous), we generated a dialog map that guides health care professionals through the many sensitive and complex patient communication issues surrounding this treatment process. Beginning with diagnosis, the dialog map includes discussion of treatment options, instruction on proper drug administration technique, and ensuring of appropriate follow-up care. At each step, we provide talking points that address the following: the patients' clinical situation; their geographic, economic, and psychological concerns; and their inclination to communicate with clinicians. We have found that involving patients, nurses, and physicians as equal partners in the treatment process optimizes treatment initiation, adherence, and persistence in acromegaly. By encouraging collaboration across the care continuum, this dialog map can facilitate identification of the treatment plan that is most likely to yield the best possible outcome.

Islet autoimmunity identifies a unique pattern of impaired pancreatic beta-cell function, markedly reduced pancreatic beta cell mass and insulin resistance in clinically diagnosed type 2 diabetes.

There is a paucity of literature describing metabolic and histological data in adult-onset autoimmune diabetes. This subgroup of diabetes mellitus affects at least 5% of clinically diagnosed type 2 diabetic patients (T2DM) and it is termed Latent Autoimmune Diabetes in Adults (LADA). We evaluated indexes of insulin secretion, metabolic assessment, and pancreatic pathology in clinically diagnosed T2DM patients with and without the presence of humoral islet autoimmunity (Ab). A total of 18 patients with at least 5-year duration of clinically diagnosed T2DM were evaluated in this study. In those subjects we assessed acute insulin responses to arginine, a glucose clamp study, whole-body fat mass and fat-free mass. We have also analyzed the pancreatic pathology of 15 T2DM and 43 control cadaveric donors, using pancreatic tissue obtained from all the T2DM organ donors available from the nPOD network through December 31, 2013. The presence of islet Ab correlated with severely impaired ß-cell function as demonstrated by remarkably low acute insulin response to arginine (AIR) when compared to that of the Ab negative group. Glucose clamp studies indicated that both Ab positive and Ab negative patients exhibited peripheral insulin resistance in a similar fashion. Pathology data from T2DM donors with Ab or the autoimmune diabetes associated DR3/DR4 allelic class II combination showed reduction in beta cell mass as well as presence of autoimmune-associated pattern A pathology in subjects with either islet autoantibodies or the DR3/DR4 genotype. In conclusion, we provide compelling evidence indicating that islet Ab positive long-term T2DM patients exhibit profound impairment of insulin secretion as well as reduced beta cell mass seemingly determined by an immune-mediated injury of pancreatic ß-cells. Deciphering the mechanisms underlying beta cell destruction in this subset of diabetic patients may lead to the development of novel immunologic therapies aimed at halting the disease progression in its early stage.

Association between impaired cardiovascular autonomic function and hypoglycemia in patients with type 1 diabetes.

OBJECTIVE: We studied the association between glycemic variability (GV) reflecting hypoglycemic stress and cardiovascular autonomic function in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: Forty-four type 1 diabetic patients (mean age 34 ± 13 years, 40% male, 86% Caucasian, mean diabetes duration 13 ± 6 years, mean hemoglobin A1c [HbA1c] 8.0 ± 1.2% [64 ± 5 mmol/mol]) without cardiovascular disease, dyslipidemia, or hypertension participated in this pilot study. Indices of GV reflective of hypoglycemic stress (low blood glucose index [LBGI] and area under the curve [AUC] for hypoglycemia) were computed using data obtained during 5-day continuous glucose monitoring. Cardiovascular autonomic neuropathy (CAN) was assessed using standardized cardiovascular reflex testing and measures of heart rate variability (HRV), which were analyzed as time and frequency domain measures. RESULTS: Both LBGI and AUC hypoglycemia had a significant negative association with the low-frequency power of HRV (r = -0.47, P = 0.002; r = -0.43, P = 0.005, respectively) and with the high-frequency power of HRV (r = -0.37, P = 0.018; r = -0.38, P = 0.015, respectively). These inverse associations persisted after adjusting for HbA1c, although they were attenuated in multivariable analysis after adjustment for age, diabetes duration, and several other covariates. CONCLUSIONS: Increased GV promoting hypoglycemic stress was associated with reduced HRV independent of glycemic control as assessed by HbA1c. These pilot data suggest that glucose variability may contribute to cardiovascular autonomic dysfunction among adults with type 1 diabetes.

Evaluation of hemoglobin A1c criteria to assess preoperative diabetes risk in cardiac surgery patients.

OBJECTIVE: Hemoglobin A1c (A1C) has recently been recommended for diagnosing diabetes mellitus and diabetes risk (prediabetes). Its performance compared with fasting plasma glucose (FPG) and 2-h post-glucose load (2HPG) is not well delineated. We compared the performance of A1C with that of FPG and 2HPG in preoperative cardiac surgery patients. METHODS: Data from 92 patients without a history of diabetes were analyzed. Patients were classified with diabetes or prediabetes using established cutoffs for FPG, 2HPG, and A1C. Sensitivity and specificity of the new A1C criteria were evaluated. RESULTS: All patients diagnosed with diabetes by A1C also had impaired fasting glucose, impaired glucose tolerance, or diabetes by other criteria. Using FPG as the reference, sensitivity and specificity of A1C for diagnosing diabetes were 50% and 96%, and using 2HPG as the reference they were 25% and 95%. Sensitivity and specificity for identifying prediabetes with FPG as the reference were 51% and 51%, respectively, and with 2HPG were 53% and 51%, respectively. One-third each of patients with prediabetes was identified using FPG, A1C, or both. When testing A1C and FPG concurrently, the sensitivity of diagnosing dysglycemia increased to 93% stipulating one or both tests are abnormal; specificity increased to 100% if both tests were required to be abnormal. CONCLUSIONS: In patients before cardiac surgery, A1C criteria identified the largest number of patients with diabetes and prediabetes. For diagnosing prediabetes, A1C and FPG were discordant and characterized different groups of patients, therefore altering the distribution of diabetes risk. Simultaneous measurement of FGP and A1C may be a more sensitive and specific tool for identifying high-risk individuals with diabetes and prediabetes.

A clinical trial of continuous subcutaneous insulin infusion versus multiple daily injections in older adults with type 2 diabetes.

OBJECTIVE: To compare the efficacy and safety of continuous subcutaneous insulin infusion (CSII) and multiple daily injection (MDI) in older adults with insulin-treated type 2 diabetes and to assess treatment satisfaction and quality of life. RESEARCH DESIGN AND METHODS: Adults (n = 107) > or =60 years of age (mean age 66 years) with insulin-treated type 2 diabetes (mean duration 16 years, BMI 32 kg/m(2), and HbA(1C) [A1C] 8.2%) were randomized to CSII (using insulin lispro) or MDI (using insulin lispro and insulin glargine) in a two-center, 12-month, prospective, randomized, controlled clinical trial. Efficacy was assessed with A1C, safety by frequency of hypoglycemia, and treatment satisfaction and quality of life with the Diabetes Quality of Life Clinical Trial Questionnaire and the 36-item short-form health survey, version 2. RESULTS: Forty-eight CSII subjects (91%) and 50 MDI subjects (93%) completed the study. Mean A1C fell by 1.7 +/- 1.0% in the CSII group to 6.6% and by 1.6 +/- 1.2% in the MDI group to 6.4%. The difference in A1C between treatment groups was not statistically significant (P = 0.20). Eighty-one percent of CSII subjects and 90% of MDI subjects experienced at least one episode of minor (self-treated) hypoglycemia (P = 0.17), and three CSII and six MDI subjects experienced severe hypoglycemia (P = 0.49). Rates of severe hypoglycemia were similarly low in the two groups (CSII 0.08 and MDI 0.23 events per person-year, P = 0.61). Weight gain did not differ between groups (P = 0.70). Treatment satisfaction improved significantly with both CSII and MDI (P < 0.0001), and the difference between groups was not statistically significant (P = 0.58). CONCLUSIONS: In older subjects with insulin-treated type 2 diabetes, both CSII and MDI achieved excellent glycemic control with good safety and patient satisfaction.