Nonenzymatic glucosylation of serum proteins in diabetes mellitus.

The extent of nonenzymatic glucosylation of serum protein in control and diabetic subjects was measured by a chemical procedure using thiobarbituric acid. A mean value of 0.81 (+/- 0.21 SD) nmol glucose per milligram serum protein was observed in the control group. Diabetics displayed elevated levels of glucosylated serum proteins, up to 4 nmol glucose per milligram protein. Glucosylation of serum protein correlated strongly with fasting blood sugar (r = 0.71), percent hemoglobin A1 (r = 0.79), and percent glucosylated albumin (r = 0.99). There was no overlap between control and diabetic groups, i.e., within 3 SD of the mean of controls. These studies indicate that the assay for glucosylated serum protein appears to be an especially sensitive indicator of the degree of hyperglycemia in diabetes.

Effect of diabetes and aging on carboxymethyllysine levels in human urine.

Carboxymethyllysine (CML) has been identified as a modified amino acid that accumulates with age in human lens proteins and collagen. CML may be formed by oxidation of fructoselysine (FL), the Amadori adduct formed on nonenzymatic glycosylation of lysine residues in protein, or by reaction of ascorbate with protein under autoxidizing conditions. We proposed that measurements of tissue and urinary CML may be useful as indices of oxidative stress or damage to proteins in vivo. To determine the extent to which oxidation of nonenzymatically glycosylated proteins contributes to urinary CML, we measured the urinary concentrations of FL and CML in diabetic (n = 26) and control (n = 28) patients. The urinary concentration of FL correlated strongly with HbA1 measurements and was significantly higher in diabetic compared with control samples (9.2 +/- 6.5 and 4.0 +/- 2.8 micrograms/mg creatinine, respectively; P less than 0.0001). There was also a strong correlation between the concentrations of CML and FL in both diabetic and control urine (r = 0.67, P less than 0.0001) but only a weakly significant increase in the CML concentration in diabetic compared with control urine (1.2 +/- 0.5 and 1.0 +/- 0.3 micrograms/mg creatinine, respectively; P = 0.05). The molar ratio of CML to FL was significantly lower in diabetic compared with control patients (0.25 +/- 0.12 and 0.43 +/- 0.16, respectively; P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Thyrotrophin-releasing hormone test: an adverse reaction.

The side effects of intravenous (IV) administration of protirelin (thyrotrophin-releasing hormone [TRH] are usually mild and transient. The loss of consciousness and apical heart tones occurred in two young patients after protirelin injection. The mechanism for the reactions in these patients is not known, but the absence of heart sounds in the presence of no palpable pulse and no obtainable blood pressure should now be included among the adverse effects that may occur after administration of protirelin IV.

Neonatal mortality in infants of diabetic mothers.

To assess the effects of an educational program emphasizing detection and tight control of maternal glucose levels during pregnancy, the management and outcome of all pregnancies complicated by diabetes mellitus delivered at a county hospital during two time periods, 1978-1980 and 1981-1983, are compared. The prevalence of diabetes during pregnancy was 1.4% between 1978 and 1980 and 2.6% between 1981 and 1983 (P less than 0.01). The perinatal death rate decreased for infants of diabetic mothers from 100 per thousand deliveries in 1978-1980 to 32 per thousand in 1981-1983 (P less than 0.02). The perinatal death rate for infants of mothers with gestational diabetes was nearly the same as the perinatal death rate for all neonates born in the state in 1981-1983. Congenital anomalies followed by stillbirths were the most frequent causes of perinatal death.

The relationship of maternal age on gestational diabetes.

This study was performed to examine the relationship between maternal age and serum glucose levels during pregnancy, and to determine if glucose screening could be eliminated in very young women without significantly compromising the detection rate of gestational diabetes mellitus. All women between the 24th and 28th wk of gestation who were followed in a university-affiliated prenatal clinic had a screening glucose level drawn 1 h after ingesting 50 g glucose. Those who had a 1-h serum glucose of greater than 150 mg/dl subsequently underwent a 3-h glucose tolerance test. There was a progressive increase in screening serum glucose levels and a significantly higher incidence of diabetes with increasing maternal age. Only 4% of women less than 20 yr had a positive screen and 8% of these had gestational diabetes. If screening had not been done in those less than 20 yr, only 5% (2/36) of women with gestational diabetes would not have been detected.

Diabetes in pregnancy and cesarean delivery.

OBJECTIVE: To evaluate the effect of diabetes during pregnancy on cesarean delivery and to determine whether the association between diabetes during pregnancy and cesarean delivery is mediated by birth weight. RESEARCH DESIGN AND METHODS: South Carolina 1993 birth certificates were matched through a unique identifier with infant and maternal hospital discharge records for the same year, yielding a total study population of 42,071 singleton births. Adjusted odds ratios (ORs) and 95% CIs were determined for the association between diabetes in pregnancy and cesarean delivery through multiple logistic regression, controlling for maternal age, race, education, number of prenatal care visits, length of gestation, birth weight, and a number of medical indications. RESULTS: Of the study population, 0.7% were pregnancies complicated by preexisting diabetes, 2.9% were pregnancies complicated by gestational diabetes, and 23.4% were cesarean deliveries. After controlling for confounders, including birth weight, cesarean delivery was strongly associated with both preexisting diabetes (OR [95% CI] 6.20 [4.47-8.61]) and gestational diabetes (1.71 [1.41-2.07]). The estimates remained essentially unchanged without birth weight in the model, and were substantially higher in analyses restricted to deliveries without common medical indications for cesarean delivery. CONCLUSIONS: Both preexisting and gestational diabetes increase the risk for cesarean delivery, independent of the effect of birth weight. The association is markedly greater among women without other medical indications for cesarean delivery. The increased risk of cesarean delivery for women with diabetes is mediated through other factors, which may include practice patterns and physician referrals to high-risk care.

Changes in blood protein glycosylation during a diabetes summer camp.

To evaluate changes in glycemic control during a 2-wk diabetes summer camp program, fasting plasma glucose (FPG), glycosylated hemoglobin (GHb), and glycosylated serum protein ( GSP ) levels were measured in a group of 36 children at the beginning and end of camp. Average FPG and GHb were unchanged during the 2-wk period, but the average decrease in GSP (7%) was significant (P less than 0.005). The results of this study indicate that a measurable improvement in diabetic control occurred in some children during the 2-wk summer camp program.

Clinical value of glycosylated serum protein and glycosylated hemoglobin levels in the diagnosis of gestational diabetes mellitus.

Glycosylated serum protein and glycosylated hemoglobin levels were compared to the oral glucose tolerance test to determine their relative sensitivity in identifying women with gestational diabetes mellitus. The mean glycosylated serum protein level (0.49 +/- SD 0.07 nmol hydroxymethylfurfural per milligram protein) of 17 pregnant women with normal glucose tolerance and the mean value (0.54 +/- SD 0.06 nmol hydroxymethylfurfural per milligram protein) of eight pregnant women with gestational diabetes mellitus were statistically different (P less than .05). However, there was such an overlap between these groups that individuals could not be categorized as normal or as having gestational diabetes mellitus on the basis of the glycosylated serum protein level. There was no difference in glycosylated hemoglobin levels between 41 women with normal glucose tolerance and 12 women with gestational diabetes mellitus. This study concluded that glycosylated serum protein and glycosylated hemoglobin determinations are not as sensitive as the glucose tolerance test in detecting gestational diabetes mellitus as it is now defined.

Changes in the fasting blood sugar after hydrochlorothiazide and potassium supplementation.

A 20% or greater rise in the fasting blood sugar occurred in 11 of 24 patients treated with 50 mg hydrochlorothiazide twice daily for six to ten weeks. The blood sugar decreased when potassium was given in conjunction with the diuretic, but the mean fasting blood sugar remained higher than pretreatment levels. There was no correlation between the percent change in the blood sugar and the per cent change in the serum K or exchangeable 42K.

Measurement of nonenzymatically glucosylated serum protein by an improved thiobarbituric acid assay.

We describe here some useful modifications of the thiobarbituric acid (TBA) assay for measurement of nonenzymatic glucosylation of serum protein. The modified assay minimizes interference by glucose without a lengthy dialysis step, and does not require an independent blank determination. These modifications should make the TBA assay more convenient for evaluating glycemic control in diabetes. Serum protein is first precipitated with cold ethanol to remove endogenous glucose. The protein is then hydrolyzed in an oxalic acid solution to release glucose as hydroxymethylfurfural (HMF). The HMF is reacted with TBA to form a chromophore which is extracted into isobutanol for spectrophotometric analysis (lambda max = 435 nm). The absorbance at 435 nm is corrected by subtracting a blank reading at 500 nm, and the nmol HMF released is determined using a standard curve prepared with pure HMF. Normal values of this assay for both adults and children are 0.38 +/- 0.10 nmol HMF/mg serum protein (means +/- 2 SD). When the assay was applied to serum samples from a group of 39 Type I diabetic children more than 90% of the children exceeded the normal range of the assay.

Fasting blood glucose levels and initiation of insulin therapy in gestational diabetes.

OBJECTIVE: To determine whether an initial fasting blood glucose determination will predict which pregnant women will need insulin in addition to dietary measures to maintain fasting glucose levels during gestation. METHODS: All women referred for management of gestational diabetes received dietary counseling and instructions for self-monitoring of blood glucose levels during fasting and at 2 hours after each meal. Insulin therapy was initiated if the fasting blood glucose value exceeded 5.8 mmol/L (105 mg/dL) on more than one occasion, the 2-hour postprandial glucose exceeded 8.3 mmol/L (150 mg/dL), or the 2-hour postprandial glucose exceeded 6.7 mmol/L (120 mg/dL) three times in a week. The use of diet alone or diet plus insulin therapy was determined by review of medical records. RESULTS: Fifty-two pregnant women with fasting blood glucose levels of less than 5.8 mmol/L (105 mg/dL) and with two or more elevated blood glucose values on a 3-hour glucose tolerance test underwent follow-up at least through the 36th week of gestation. In 21 patients, insulin therapy was initiated in addition to diet. Two of five women with an initial fasting glucose level of less than 4.4 mmol/L (80 mg/dL) required insulin, and 8 of 24 women with fasting levels of 5.3 to 5.8 mmol/L (96 to 105 mg/dL) eventually needed insulin. CONCLUSION: The height of the fasting blood glucose level in women with gestational diabetes does not separate those who will maintain blood glucose levels in the targeted therapeutic range on diet alone from those who will need insulin. Therefore, all women with gestational diabetes need to participate in self-monitoring of blood glucose levels.

Meaning of illness and health outcomes in type 1 diabetes.

OBJECTIVE: To determine whether a relationship exists between the meaning attributed to type 1 diabetes and mental and physical health outcomes. METHODS: The study sample consisted of 49 adults with type 1 diabetes. Each participant voluntarily agreed to complete the Meaning of Illness Questionnaire (MIQ), the Short Form-36 Health Survey (SF-36), and the Diabetes Health Survey. Multivariant analysis of covariance was used to determine the relationships among the MIQ and SF-36, a history of depression, hemoglobin A1c, and other demographic variables. RESULTS: The meaning attributed to illness predicted health outcomes. Specifically, the impact of illness (MIQ subscale 1; P = 0.030) predicted SF-36 physical functioning, bodily pain, and general mental health; the degree of stress (MIQ subscale 3; P = 0.008) predicted SF-36 general physical health, vitality, and general mental health. Conversely, a history of depression (P = 0.014) and high hemoglobin A1c (P = 0.039) predicted a more negative meaning attributed to illness. CONCLUSION: The meaning attributed to illness varies with physical and mental health. In addition, physical and mental health outcomes and hemoglobin A1c, a measure of mean blood glucose, affect the meaning attributed to diabetes. The findings in this study support a bidirectional relationship between the meaning attributed to illness and health outcomes in patients with type 1 diabetes.

Muscle infarction in diabetes: clinical manifestations and course.

OBJECTIVE: To characterize the initial manifestations and course of muscle infarction in diabetes, a rarely diagnosed condition. METHODS: We describe two patients with this disorder and review the clinical characteristics of previously reported cases. RESULTS: Usually, the initial complaint in patients with muscle infarction in diabetes is swelling of the thigh or calf that has evolved over days to months. Biopsy of the muscle is often necessary for diagnosis and reveals extensive muscle necrosis. Although the pathogenesis is unknown, hypercoagulability may have a role. Bilateral involvement and recurrent disease are common. Treatment is supportive; our patients required narcotics for alleviation of pain. CONCLUSION: Muscle infarction in diabetes may mimic thrombophlebitis, soft tissue infection, or a neoplasm. Medical evaluation may be directed toward these entities, and the diagnosis of a diabetes-associated disorder may be completely overlooked. The presence of atraumatic swelling of an extremity in a patient with diabetes should suggest diabetes-related muscle infarction.

Speaking and interruptions during primary care office visits.

BACKGROUND: Patients and physicians value effective communication and consider it an essential part of the medical encounter. This study examined physician-patient communication patterns, and interruptions in communication, during patient visits with family practice and internal medicine residents. METHODS: Observational data obtained from 60 routine primary care office visits included the time that resident physicians and patients spoke and the number and types of interruptions. A total of 22 family practice and internal medicine residents participated, 9 from family practice and 13 from internal medicine. RESULTS: Patients spoke, uninterrupted, an average of 12 seconds after the resident entered the room. One fourth of the time, residents interrupted patients before they finished speaking. Residents averaged interrupting patients twice during a visit. The time with patients averaged 11 minutes, with the patient speaking for about 4 minutes. Computer use during the office visit accounted for more interruptions than beepers. Verbal interruptions, a knock on the door, beeper interruptions, and computer use all interfered with communication, and increased frequency of interruptions are associated with less favorable patient perceptions of the office visit. Female residents interrupted their patients less often than did male physicians. All residents interrupted female patients more often than male patients. Early and increased interruptions were associated with patients' perception that they should have talked more. Third-year residents interrupted patients less frequently than did first-year residents. CONCLUSIONS: Numerous interruptions occurred during office visits. Gender was associated with the pattern of interruptions. Physicians frequently interrupted patients before the patients were finished speaking. Computer use also interrupted physician-patient communication.

Type 2 diabetes: stepped-care approach to patient management.

An oral antidiabetic medication and/or insulin in addition to exercise and a nutritious meal plan form the basis for treatment of type 2 diabetes. Blood glucose self-monitoring helps guide therapeutic decisions. Therapy needs modification when glycated hemoglobin levels exceed 8%. Initially pharmacologic therapy may include any one of the following: a sulfonylurea, metformin, acarbose, troglitazone, or insulin. If monotherapy does not maintain near-normoglycemia, combined oral antidiabetic medication or insulin may bring glucose levels into the therapeutic range. If combination therapy does not achieve target goals, then insulin given twice daily or more often becomes necessary.

Hypothyroidism in the elderly. When symptoms are not a 'normal' part of aging.

Clinical findings alone may not lead to prompt diagnosis of hypothyroidism in elderly patients. Therefore, routine thyroid function tests may be warranted in older patients, especially women. Serum thyrotropin (TSH) is the most sensitive marker for hypothyroidism, although the test is more costly than that for serum thyroxine (T4). Patients with overt hypothyroidism who have elevated TSH and low T4 levels require replacement therapy. In addition, patients who have a TSH level higher than 20 microU/mL or who have a mildly elevated TSH level and high titers of antithyroid antibodies may benefit from prophylactic treatment. The usual recommended replacement dose is 0.05 to 0.1 mg/day of levothyroxine sodium (Levothroid, Synthroid).

Graves' disease. Manifestations and therapeutic options.

Graves' disease is the most common cause of hyperthyroidism. Clinical features include thyroid enlargement, eye signs, tachycardia, heat intolerance, emotional lability, weight loss, and hyperkinesis. Three modes of therapy are available. The preferences of the patient and physician are usually prime considerations in devising the therapeutic plan. Radioactive iodine is the most frequently used and safest method of treatment for adults. Antithyroid drugs are preferred for children and pregnant women. Surgery is usually reserved for patients in whom the other forms of treatment are not acceptable. Considerable patient education during the decision-making process enhances the success of the therapeutic plan.

Demystifying hypoglycemia. When is it real and how can you tell?

Contrary to popular belief, hypoglycemia is an infrequently encountered condition and its presence is questionable until confirmed by appropriate tests. In ambulatory patients, blood glucose levels obtained during intake of a normal diet are more reliable than those obtained during a glucose tolerance test. If the blood glucose is actually abnormally low and the other two criteria of hypoglycemia are also satisfied, a search for the cause is in order. In hospitalized patients, excessive doses of insulin or oral hypoglycemic agents, the effect of drugs, or chronic renal failure are the most common causes of hypoglycemia. If these factors are absent, another chronic illness known to cause hypoglycemia may be the source. If the cause is still obscure, a thorough evaluation of the endocrine status is warranted.