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Biomedical subjects

R M Bergenstal

Publications and source records attributed to R M Bergenstal.

17 recordsLinked to original sources

Characterizing blood pressure control in individuals with Type 2 diabetes: the relationship between clinic and self-monitored blood pressure.

AIMS: To determine the relationship between blood pressure (BP) measurement in the clinic and self-monitored blood pressure (SMBP); and to evaluate the accuracy of self-reported data in patients with Type 2 diabetes treated intensively for hypertension. METHODS: Seventy subjects had baseline and 1-week follow-up clinic BP measured using an Omron 907 automated device. During a contemporaneous 14-day period these subjects measured their BP at least four times each day using an Omron IC semiautomatic portable monitor which, unknown to them, contained an onboard memory capable of storing BP with corresponding time and date. RESULTS: There was no significant difference between mean clinic and mean self-monitored BP. Correlations between clinic BP and SMBP were r=0.61 (P<0.0001) for systolic BP and r=0.69 (P<0.0001) for diastolic BP. Clinic BP classified 56 subjects as uncontrolled hypertension (BP > or = 130/80 mmHg, adjusted for diabetes) and 14 subjects as controlled hypertension. Using World Health Organization-International Society of Hypertension criteria for SMBP (> or = 125/75 mmHg), 55 cases of clinic classified uncontrolled hypertension were confirmed, resulting in 98% sensitivity. Clinic and SMBP agreed in one case of controlled hypertension, resulting in 7% specificity. For all subjects, the median percent of values exceeding SMBP criteria for controlled hypertension was systolic 92% and diastolic 70%. Self-reporting precision averaged 89+/-10% (range 45-100%); under-reporting was 25+/-16% (ranging from 0 to 56%) and over-reporting was 12+/-15% (ranging from 0 to 46%). The overall logbook mean was not significantly different from the downloaded data from the Omron IC(R) monitors. CONCLUSIONS: SMBP was able to identify 13 patients with uncontrolled hypertension who, by clinic BP measurement, had been classified as controlled.

Adult↗

Use of an automated device for alternative site blood glucose monitoring.

OBJECTIVE: To evaluate the accuracy, comfort, and ease of use of a new automated device for blood glucose monitoring using the arm as an alternative sampling site. RESEARCH DESIGN AND METHODS: These studies use an automated hand-held device that applies a small vacuum, lances the skin, transfers blood onto an electrochemical test strip, and measures glucose. Patients who had type 1 or type 2 diabetes and had received no prior training using this device were recruited from five diabetes clinics. Testing was performed by the patients using this device and by trained healthcare professionals. Blood glucose was measured by 354 patients: from the arm using the device, from the finger using a laboratory reference instrument, and from the finger using the device via the secondary test port. Each patient completed a questionnaire rating the level of pain and ease of use of the device. RESULTS: Blood glucose results in samples obtained from the arm with the automated device agreed well with finger-stick plasma glucose results using a reference instrument (regression slope 0.98, intercept 0.01 mmol/l [0.1 mg/dl], r = 0.96). Error grid analysis showed that 100% of the measurements fell within zones A and B. In the survey, 60% of the patients reported that arm testing with the automated device was "painless;" another 31% of the patients stated that it was "much less painful," and 6% of patients considered using the device "less painful" than finger-stick testing. In a survey containing 15 questions for rating the ease of use with a scale of 1 to 6, the overall mean rating was 5.5. CONCLUSIONS: The automated device is easy to use and provides accurate glucose results; 97% of the patients found it less painful than finger-stick testing.

Adolescent↗

Comprehensive management of patients with type 2 diabetes: establishing priorities of care.

Type 2 diabetes is a complex metabolic disorder characterized by elevated blood glucose levels and a marked increase in the risk of cardiovascular disease (CVD). The increased CVD risk is caused by a unique cluster of metabolic abnormalities, including dyslipidemia, hypertension, insulin resistance, and hyperglycemia. To reduce the risk of cardiovascular complications in patients with type 2 diabetes, comprehensive management of risk factors is essential. Aggressive treatment of dyslipidemia and hypertension is known to benefit patients with type 2 diabetes. In addition, intensive glycemic control and targeted treatment of insulin resistance can further reduce the enormous burden of CVD in this high-risk population. Increasing evidence suggests that insulin resistance is one of the earliest markers of risk for both CVD and diabetes, and it is known that insulin resistance alone can significantly increase the risk of CVD. Type 2 diabetes and insulin resistance are both associated with disordered lipid metabolism, manifest in elevated triglyceride levels, low levels of high-density lipoprotein cholesterol, and small, dense low-density lipoprotein cholesterol particles. Patients with type 2 diabetes and insulin resistance have an increased risk of hypertension, which further contributes to their CVD risk. Each of these factors can also contribute to the risk of microvascular disease. To ensure that patients with type 2 diabetes receive comprehensive, high-quality care, specific standards have been developed. These standards can help providers establish clear treatment targets, identify specific priorities of care, and use therapies of known efficacy to reduce the risk of complications. This review summarizes the current standards of care for patients with type 2 diabetes, with an emphasis on treatments that reduce the cardiovascular risk factors. Using a case study approach, it reviews the essential components of diabetes care and proposes a rational approach to these complex cases--an approach that should result in consistent, high-quality care.

Adult↗

Diabetic ketoacidosis. How to treat and, when possible, prevent.

Treatment and prevention of diabetic ketoacidosis (DKA) should be guided by an understanding of the metabolic decompensation that occurs in this medical emergency. The primary cause of DKA is insulin deficiency, which may be precipitated by infection or other forms of stress. As hyperglycemia exceeds the renal threshold, it leads to osmotic diuresis, electrolyte loss, and eventually dehydration. Treatment, therefore, consists primarily of insulin administration and replacement of fluid and electrolytes. Likewise, prevention hinges on avoiding insulin deficiency by tight control of blood glucose levels and compensation for stress. Because of the metabolic derangements of DKA, some laboratory tests can be misleading and need to be carefully interpreted.

Amylases↗

Diarrhea in streptozocin-treated rats. Loss of adrenergic regulation of intestinal fluid and electrolyte transport.

Diarrhea was noted in rats with streptozocin-induced chronic diabetes. We have investigated the possibility that this diarrhea is a consequence of altered neuronal control of water and electrolyte absorption in the intestinal epithelium. In particular, we examined noradrenergic control because alpha-2-adrenergic agonists are known to stimulate intestinal fluid absorption. When compared with nondiabetic littermates, chronically diabetic rats exhibited significant impairment of fluid absorption by the ileum and colon, but not the jejunum. This impairment of intestinal fluid absorption was not found in either insulin-treated or untreated acutely diabetic (7 d) animals. Mucosal histology appeared normal in all of the above groups. Mucosal norepinephrine stores in the jejunum and ileum of chronically diabetic rats were estimated in vitro by the short-circuit current (Isc) response to tyramine, an agent that effectively releases stored norepinephrine. Pargyline was added to inhibit enzymatic destruction of the added tyramine. In chronically diabetic rats, the Isc response to tyramine was significantly decreased in ileum, but not in jejunum. However, when these responses were expressed as a fraction of the maximal Isc tissue response to exogenously added epinephrine, significant decreases were noted in both ileum and jejunum. In tissues from acutely diabetic rats, Isc responses to tyramine and epinephrine were no different from controls. When sympathetic denervation was produced in nondiabetic rats by treatment with 6-OH-dopamine, the pattern of impaired fluid absorption that developed was the same as that observed in chronically diabetic rats. We conclude that impaired intestinal mucosal absorption of fluid and electrolytes slowly develops in rats made diabetic with streptozocin and that this absorptive impairment is due to a loss of normally present noradrenergic innervation of enterocytes.

Animals↗

Observations on control of glycemia with conventional insulin therapy or continuous subcutaneous insulin infusion.

Determination of glycemic differences between groups treated with continuous subcutaneous insulin infusion (CSII) or conventional insulin therapy (CIT) was central to the major objective of the study. Assessment of glycemia was based on 24-h inhospital profiles of plasma glucose; pre- and postprandial and bedtime (seven time points) diurnal profiles performed monthly on outpatient samples; and glycosylated hemoglobin (HbA1) measured bimonthly at each center. The correlation between plasma glucose determinations in the central laboratory and in local laboratories was 0.988. Significance of differences between treatments was by analysis of variance and least-squares regression. At baseline, mean inhospital plasma glucose and HbA1 concentrations and insulin dosages were identical in the groups randomized to CSII or CIT. A prompt decrement of indices of glycemic control during CSII was observed such that mean decrements sustained over the 8-mo treatment period in home and in hospital plasma glucose profiles and HbA1 relative to values obtained during CIT (P less than 0.0001). The likelihood of CSII-treated patients achieving glycemic indices within the normal range was increased. The standardization of the mean and the M-value calculated from inhospital glucose profiles during CSII and CIT at 4 and 8 mo indicated that there was less plasma glucose fluctuation during CSII. The method of pooling standardized local HbA1 measurements from the six centers appeared to be an adequate substitute for centrally performed HbA1 determinations. Advantages of inhospital plasma glucose measurements in terms of accuracy and ability to obtain nocturnal samples contrasted with the likelihood of increased realism and superior correlation with HbA1 in home-obtained samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

Observations on C-peptide and free insulin in the blood during continuous subcutaneous insulin infusion and conventional insulin therapy.

As part of a multicenter trial, 70 individuals with insulin-dependent diabetes were randomized to either conventional insulin therapy (CIT) or continuous subcutaneous insulin infusion (CSII). In order to standardize patient selection in the six participating centers, one of the eligibility criteria was the demonstration that each patient had no residual endogenous insulin secretion as assessed by plasma C-peptide determinations. The patients were of average (+/- SEM) age of 33.0 +/- 1.6 yr, had had diabetes for a mean (+/- SEM) duration of 17.4 +/- 1.1 yr, and had both fasting and postglucagon stimulation C-peptide values of less than 0.1 pmol/ml, consistent with clinically insignificant endogenous insulin secretion. There was no change in C-peptide response at 4 or 8 mo compared with baseline values, whether or not the patient's glucose control remained unchanged (CIT group) or significantly improved to near-normoglycemia (CSII group). In a subgroup of 34 patients at three centers, the 24-h mean glucose concentration was significantly lower in the CSII group compared with the CIT group at 4 mo (126 +/- 10 versus 176 +/- 14 mg/dl) and at 8 mo (121 +/- 5 versus 183 +/- 15 mg/dl) (P less than 0.005). Although the 24-h mean serum free immunoreactive insulin levels were shown to be no different at baseline (27.4 +/- 3.8 versus 26.2 +/- 3.1 microU/ml) or after 4 mo (22.5 +/- 3.2 versus 25.6 +/- 3.2) or 8 mo (26.5 +/- 3.4 versus 28.8 +/- 3.4) of CIT or CSII therapy, respectively, the mean increase of free insulin concentrations in relation to the main meals was greater in the CSII group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Dietary practices of persons with diabetes during insulin pump therapy.

Eating behaviors and diet composition were investigated in 15 individuals with insulin-dependent diabetes treated by continuous subcutaneous insulin infusion (CSII). Glycemic control was significantly improved and was near normal during pump treatment. Patients were interviewed with the use of a structured questionnaire composed of multiple question formats to document dietary practices and to identify changes from conventional therapy. Mealtimes were varied considerably on both conventional and pump therapy (as much as 110 +/- 19 and 126 +/- 20 minutes, respectively), but mealtime delays were reported to be manageable while the patients were using the pump. The practices of eating larger meals or additional snacks compensated for by extra insulin significantly increased during CSII therapy. Partly as a consequence of such practices, patients experienced a significant weight gain of 7.2 +/- 2 lb during pump treatment (p less than .005). Clearly, prospective studies are needed to determine the acceptable degree of dietary flexibility and the optimal management of diet during insulin pump therapy.

Adult↗

Familial hyperinsulinemia due to a structurally abnormal insulin. Definition of an emerging new clinical syndrome.

We have identified a patient with mild diabetes, marked fasting hyperinsulinemia (89 to 130 microU of insulin per milliliter), and a reduced fasting C-peptide: insulin molar ratio of 1.11 to 1.50 (normal, greater than 4). The patient responded normally to exogenous insulin. However, her endogenous immunoreactive insulin showed reduced biologic activity during a glucose-clamp study with hyperglycemia and a reduced ability to bind to the insulin receptor and stimulate glucose transport in vitro. Family studies showed that five additional relatives in three generations had variable degrees of glucose intolerance, marked hyperinsulinemia, and a reduced peripheral C-peptide:insulin molar ratio. Restriction-endonuclease cleavage of DNA isolated from circulating leukocytes in the patient and in family members with hyperinsulinemia revealed loss of the MboII recognition site in one allele of the insulin gene--consistent with a point mutation at position 24 or 25 in the insulin B chain. Other studies using high-pressure liquid chromatography and detailed gene analysis have identified the defect as a serine for phenylalanine substitution at position 24 of the insulin B chain. The secretion of a structurally abnormal insulin should be considered in patients with hyperinsulinemia who respond normally to exogenous insulin and have a reduced C-peptide:insulin molar ratio. Glucose tolerance may range from relatively normal to overtly diabetic.

Adult↗

The metabolic effects of biosynthetic human proinsulin in individuals with type I diabetes.

To assess the significance of deficiency of circulating proinsulin in patients with type I diabetes mellitus, we studied the metabolic effects of biosynthetic human proinsulin in 24 patients. After withdrawing insulin, an infusion of proinsulin to physiological plasma levels did not prevent elevations of plasma glucose or beta-hydroxybutyrate. During steady state infusions of insulin and proinsulin, 13.7 times the steady state plasma level of proinsulin compared to insulin was required to maintain euglycemia. This finding indicates that proinsulin is approximately 7.3% as biologically active as insulin on a molar basis in maintaining glucose control. The MCRs of insulin and proinsulin during these steady state infusions were 12.5 +/- 2.2 (+/- SEM) and 2.62 +/- 0.33 ml/kg X min, respectively. After maintaining euglycemia overnight with an infusion of insulin or proinsulin and then acutely stopping these infusions, the rise in plasma glucose after proinsulin was delayed significantly compared to insulin, consistent with proinsulin's slower clearance. Further studies are necessary to determine whether biosynthetic human proinsulin has a specific role in the treatment of diabetes.

Blood Glucose↗

Glucose counterregulation in patients after pancreatectomy. Comparison with other clinical forms of diabetes.

Glucose and counterregulatory hormone responses to a high-dose (1.7 mU/kg/min) insulin infusion were studied in 6 patients who had undergone total pancreatectomy, and the results were compared with those of normal controls and patients with other clinical forms of diabetes. The maximum increase in the plasma glucagon concentration during hypoglycemia in the pancreatectomized patients (5 +/- 5.6 pg/ml) was less than in normals (121 +/- 22 pg/ml). Type I diabetic subjects (28 +/- 14 pg/ml), and insulin-treated diabetic subjects of recent onset (36 +/- 12 pg/ml) also had reduced responses, while responses were normal in type II diabetic subjects (102 +/- 26 pg/ml). The epinephrine response to the hypoglycemic stimulus was reduced after pancreatectomy (278 +/- 81 pg/ml) and in type I diabetic subjects (628 +/- 244 pg/ml), but was not different from control (858 +/- 126 pg/ml) in type II and recent-onset diabetic patients. There was considerable overlap in counterregulatory hormone responses in individual patients with and without autonomic neuropathy and with normal or undetectable fasting C-peptide concentrations. While the control subjects all experienced symptoms of hypoglycemia within a narrow range of plasma glucose concentrations (35-46 mg/dl), five of the diabetic subjects experienced symptoms of hypoglycemia at plasma glucose levels of greater than or equal to 55 mg/dl, and five had no subjective awareness of hypoglycemia despite plasma glucose levels less than 30 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lack of glucagon response to hypoglycemia in type I diabetics after long-term optimal therapy with a continuous subcutaneous insulin infusion pump.

Counterregulatory hormonal responses were studied in six patients after 4-18 mo treatment with a continuous subcutaneous insulin infusion pump. In response to insulin-induced hypoglycemia, significant increases in epinephrine, norepinephrine, cortisol, and growth hormone were measured in all subjects, while in five of the six patients glucagon levels did not increase at all. The persistence of these abnormal glucagon responses despite long-term optimal glucose control suggests that they are not due to hyperglycemia per se, but are due rather to a specific alpha cell abnormality. The high incidence of asymptomatic hypoglycemia in these patients emphasizes that caution is necessary to avoid serious hypoglycemia when striving for near-normal glucose control with insulin infusion pump therapy.

Adult↗

Multiple androgenic abnormalities, including elevated free testosterone, in hyperprolactinemic women.

To investigate the basis of the hirsutism and elevated plasma dehydroepiandrosterone (DHA) and/or DHA sulfate (DHAS) in hyperprolactinemic women, we measured androgen binding parameters and an extensive profile of plasma androgens in normal (NL) and hyperprolactinemic women (HYPRL). ACTH tests and dexamethasone (dex) suppression tests were performed in subgroups. Free testosterone levels were higher in HYPRL (13.1 +/- 23.3 vs. 7.18 +/- 0.72 pg/ml; P less than 0.025), although total testosterone was comparable. This disparity was related to plasma testosterone-estradiol-binding globulin (TEBG) levels being one third lower in HYPRL (mean +/- SE, 27.4 +/- 4.0 nM) than in NL (41.2 +/- 3.7 nM; P less than 0.0125). Less striking elevations of plasma DHAS, androstenedione, and 11-deoxycortisol were found in HYPRL. Plasma total dihydrotestosterone [17 beta-hydroxy-5 alpha-androstan-3-one (tDHT)] was nearly 30% lower in HYPRL (11.2 +/- 2.6 ng/dl) than in NL (15.6 +/- 1.3 ng/dl; P less than 0.025), whereas free DHT was normal. Ratios of tDHT to precursors were lower in HYPRL (P less than 0.005). After ACTH stimulation, hyperresponsiveness of 17-hydroxyprogesterone and androstenedione were observed. Apparent adrenal enzyme efficiencies, judged from post-ACTH product to precursor ratios, were normal in HYPRL with one exception: the ratio of tDHT to total testosterone at 4 h was lower (P less than 0.05). Dex suppression normalized androgens and obliterated the abnormal tDHT to precursor ratios. These findings suggest an ACTH dependency of the abnormalities. In summary, we find that about 40% of HYPRL have an androgenic abnormality, and the most characteristic abnormality is an elevated free testosterone level (abnormal in 43%). Depressed TEBG and high DHAS levels were found with lesser frequency (19-21%). The plasma tDHT concentration was low, both in absolute terms and relative to its precursors. Dex suppressibility of the hyperandrogenemia was also observed. We postulate that PRL may exert multiple effects on steroid secretion and metabolism. Possibilities include the inhibition of the TEBG level.

Adolescent↗

Familial hyperproinsulinemia: partial characterization of circulating proinsulin-like material.

Familial hyperproinsulinemia is an autosomal dominant defect that is associated with strikingly elevated levels of serum proinsulin-like material. Our studies show that trypsin converts familial hyperproinsulinemia proinsulin to insulin more slowly than it converts a 131I-labeled porcine proinsulin marker. Molar yields of insulin indicated that the material may be an intermediate proinsulin. Studies with two human C-peptide antisera that differ in their relative immunoreactivity with human C-peptide and proinsulin showed that the two antisera reacted equally with familial hyperproinsulinemia proinsulin, suggesting that it is a partially cleaved proinsulin intermediate. Sulfitolysis of highly purified material to break the inter- and intra-chain disulfide bridges and subsequent adsorption on a specific B-chain antibody covalently bound to Sepharose beads showed that the C-peptide was still connected to the B-chain. These data indicate that familial hyperproinsulinemia proinsulin is normally cleaved at the C-peptide-A-chain linkage site. A structural abnormality appears to underlie familial hyperproinsulinemia proinsulin, which impairs its cleavage at the B-chain-C-peptide linkage site.

Amino Acid Sequence↗

Optimization of insulin therapy in patients with type 2 diabetes.

OBJECTIVE: To analyze emerging trends in effective utilization of insulin in the treatment of type 2 diabetes. METHODS: A systematic management plan and requirements for successful insulin therapy in patients with type 2 diabetes are outlined. RESULTS: The key to successful management of type 2 diabetes with insulin therapy is the use of adequate amounts of insulin and a bolus-to-basal insulin ratio of 1:1. Patient education about the progressive nature of the disease and the importance of self-monitoring of blood glucose is essential. The most effective method of sustaining normal blood glucose levels is to mimic the physiologic response to intake of food and thereby control postprandial glycemic excursions. Rapid-acting insulin lispro is useful in this effort. In the development of effective insulin regimens, one option is use of an insulin sensitizer in combination with bedtime NPH insulin. CONCLUSION: Because of deteriorating beta cell function, insulin deficiency results and usually necessitates administration of exogenous insulin in patients with type 2 diabetes. The goal of insulin treatment of type 2 diabetes is to achieve near-normal glycemic control. The insulin secretory defect progresses over time; thus, therapy must be continually matched to the underlying pathophysiologic defects.

Diabetes Mellitus, Type 2↗