Clinical implications of amylin and amylin deficiency.

PURPOSE: This paper presents an overview of the physiology of glycemic control and the mechanisms of amylin deficiency in people with diabetes. Benefits of replacement therapy with both pramlintide and insulin are discussed. METHODS: The discovery of the pancreatic beta-cell hormone amylin, which is cosecreted with insulin in response to hyperglycemia, has prompted a reanalysis of the mechanisms underlying the control of glucose homeostasis. A review of the current literature on amylin and amylin deficiency provides the basis of this reanalysis, with a discussion of the clinical implications for people with diabetes. RESULTS: Amylin appears to work with insulin to regulate plasma glucose concentrations in the bloodstream, suppressing the postprandial secretion of glucagon and restraining the rate of gastric emptying. People with diabetes have a deficiency in the secretion of amylin that parallels the deficiency in insulin secretion, resulting in an excessive inflow of glucose into the bloodstream during the postprandial period. CONCLUSIONS: While insulin replacement therapy is a cornerstone of diabetes treatment, replacement of the function of both amylin and insulin may allow a more complete restoration of the normal physiology of glucose control.

A biopsychosocial model of glycemic control in diabetes: stress, coping and regimen adherence.

This study examines stress, coping, and regimen adherence as determinants of chronic and transient metabolic control in diabetes. We also examine the interaction of biologic vulnerability and psychosocial risk factors to see if Type 1 (insulin dependent diabetes mellitus) or Type 2 (noninsulin dependent diabetes mellitus) diabetes had greater responsiveness to psychosocial risk factors. Analyses of data from insulin-treated adults with Type 1 (N = 57) and Type 2 (N = 61) diabetes supported the biopsychosocial model. For Type 1 diabetes, self-controlling persons had better glycemic control and emotional persons had worse (because of differences in stress). All of these associations were mediated by regimen compliance. For Type 2 diabetes, self-controlling persons had better glycemic control for reasons other than regimen compliance. There was an interaction between biologic and psychosocial factors, with psychosocial factors accounting for more variance in glycemic control within Type 1 patients. Stable psychosocial resources (i.e., education, being married, and positive coping styles) were associated with better chronic glycemic control, while stress and regimen nonadherence were associated with worse transient glycemic control.

Diabetes and pregnancy. Factors associated with seeking pre-conception care.

OBJECTIVE: To define sociodemographic characteristics, medical factors, knowledge, attitudes, and health-related behaviors that distinguish women with established diabetes who seek pre-conception care from those who seek care only after conception. RESEARCH DESIGN AND METHODS: A multicenter, case-control study of women with established diabetes making their first pre-conception visit (n = 57) or first prenatal visit without having received pre-conception care (n = 97). RESULTS: Pre-conception subjects were significantly more likely to be married (93 vs. 51%), living with their partners (93 vs. 60%), and employed (78 vs. 41%); to have higher levels of education (73% beyond high school vs. 41%) and income (86% > $20,000 vs. 60%); and to have insulin-dependent diabetes mellitus (IDDM) (93 vs. 81%). Pre-conception subjects with IDDM were more likely to have discussed pre-conception care with their health care providers (98 vs. 51%) and to have been encouraged to get it (77 vs. 43%). In the prenatal group, only 24% of pregnancies were planned. Pre-conception patients were more knowledgeable about diabetes, perceived greater benefits of pre-conception care, and received more instrumental support. CONCLUSIONS: Only about one-third of women with established diabetes receive pre-conception care. Interventions must address prevention of unintended pregnancy. Providers must regard every visit with a diabetic woman as a pre-conception visit. Contraception must be explicitly discussed, and pregnancies should be planned. In counseling, the benefits of pre-conception care should be stressed and the support of families and friends should be elicited.

Central pontine myelinolysis and pontine lesions after rapid correction of hyponatremia: a prospective magnetic resonance imaging study.

The rate at which profound hyponatremia should be corrected is the focus of a recent clinical debate. We prospectively studied neurological outcomes with serial magnetic resonance imaging in 13 hyponatremic subjects with serum sodium concentrations of less than 115 mmol/L (mean initial serum sodium concentration, 103.7; range, 93-113 mmol/L). All subjects were corrected to mildly hyponatremic levels at 24 hours and ultimately underwent an increase in serum sodium concentration of 25 mmol/L without development of hypernatremia. Magnetic resonance imaging revealed the development of pontine lesions in 3 patients. The correction rate of hyponatremia over the first 24 hours was significantly faster in patients with pontine lesions (mean +/- SD, 1.25 +/- 0.4 mmol/(L . hr) versus 0.74 +/- 0.3 mmol/(L . hr); p less than 0.05). Initial sodium concentration was also significantly lower in the pontine lesion group (97.3 +/- 6.7 vs 105.6 +/- 5.2 mmol/L, p less than 0.05). We conclude that the correction rate of hyponatremia plays a significant role in the pathogenesis of pontine lesions in individuals with profound hyponatremia who undergo large increases in sodium concentration as a result of severe initial hyponatremia.

Evaluation of the insulin jet injector as a potential source of infection.

In recent years jet injection of insulin has been widely used by patients with diabetes mellitus. Jet injectors may become contaminated by bacteria because of repeated use without cleaning; cleansing every 2 weeks is recommended. We investigated the occurrence of bacterial contamination by culturing jet injectors in everyday use by 19 patients with diabetes. Swabs from the interior chambers were cultured on blood agar plates. Only one of 20 cultures yielded bacterial growth, and the organism recovered was a presumed contaminant that could not be identified as any common pathogen. No study patient, nor any of more than 70 patients whom we instructed in jet injection, showed any clinical evidence of infection attributable to jet injector use. Jet injectors are unlikely to become colonized by bacteria or to cause infection in patients using them for insulin administration. The low rate of colonization may be due to the antibacterial preservatives added to commercial preparations of insulin. Additional data based on larger numbers of patients would be useful in further clarifying the risk of infection associated with jet injectors.

The diabetes control and complications trial (DCCT): the trial coordinator perspective. Report by the DCCT Research Group.

We present an overview of the role of the trial coordinator in the Diabetes Control and Complications Trial (DCCT). The DCCT is a multicenter clinical trial designed to examine the effects of two different diabetes treatment regimens on the appearance and progression of the early vascular complications of IDDM. Although the specific responsibilities assumed by the trial coordinators differ from center to center, in general they include administration, recruitment, eligibility testing, and patient management. The trial coordinator's role has evolved with the needs of the DCCT, and may serve as a model for other large multicenter trials.

Hypoglycemia after administration of somatostatin analog (SMS 201-995) in metastatic carcinoid.

SMS 201-995 (Sandoz Pharmaceuticals, East Hanover, NJ) is a synthetic peptide analog of native somatostatin that has been used to relieve symptoms caused by neuroendocrine tumors. Reports have described an insulin suppressive effect of SMS 201-995 that results in elevations of blood glucose. We report a patient with a metastatic small bowel carcinoid and renal failure in whom mild symptomatic hypoglycemia occurred 30 to 60 minutes after SMS 201-995 administration. No increase in insulin or decreases in glucagon, cortisol, or catecholamines were observed during these hypoglycemic episodes. Elevated levels of growth hormone fell gradually following SMS 201-995 administration and did not temporally correspond to the 30- to 60-minute nadir of blood glucose. However, SMS 201-995 levels peaked during this 30- to 60-minute period. As clinical experience with this drug broadens, patients whose glucose control is dependent on counter-regulatory hormones should be monitored for the possibility of hypoglycemia.