Hemoglobin A1 Concentration Research Articles

Diabetes with poor-control HbA1c is cardiovascular disease ‘risk equivalent’ for mortality: UK Biobank and Hong Kong population-based cohort study

IntroductionType 2 diabetes mellitus (T2DM) has traditionally been considered a coronary heart disease ‘risk equivalent’ for future mortality, but significant heterogeneity exists across people with T2DM. This study aims to...

Metabolic Safety of Growth Hormone in Type 1 Diabetes and Idiopathic Growth Hormone Deficiency

To evaluate metabolic consequences of growth hormone (GH) treatment in children with type 1 diabetes. This study is an analysis of metabolic changes in 37 patients with childhood-onset GH deficiency and type 1 diabetes, documented in the Diabetes Patienten Verlaufsdocumentationsystem database. Main outcome measures were changes in hemoglobin A1c and daily insulin requirements during GH therapy in children with GH deficiency and type 1 diabetes compared with a large cohort of adolescents with type 1 diabetes. Thirty-seven patients with type 1 diabetes and a diagnosis of idiopathic GH deficiency after onset of diabetes were compared with 48856 patients with type 1 diabetes. After adjustment for age, sex, duration of diabetes, and migration background, a significant difference in mean daily insulin requirement was seen between the 2 groups (1.0 IU/kg/day in subjects with GH deficiency and type 1 diabetes vs 0.85 IU/kg/day in controls; P < .01) and height-SDS (-2.0 in subjects with GH deficiency and diabetes vs +0.03 in controls; P < .0001). There was no significant between-group difference in hemoglobin A1 concentration, however (8.1% ± 1.4% in patients with GH deficiency and type 1 diabetes vs 8.2% ± 1.7% in those with type 1 diabetes only; P > .05). An increased daily insulin requirement should be considered in patients with type 1 diabetes treated with GH. With adequate adaptation of insulin dosage, metabolic control is not impaired during GH treatment.

Induction of Transient Proteinuria, Hematuria, and Glucosuria by Ethanol Consumption in Japanese Alcoholics

Urinalysis was carried out in 231 inpatients with alcohol dependence syndrome (215 males and 16 females). Fifty-nine patients (25.5%) showed proteinuria, 97 (42.0%) showed glucosuria, and 62 patients (26.8%) showed hematuria on admission. A total of 135 out of 231 patients (58.4%) showed abnormal urinalysis. Proteinuria was related to high blood pressure, high serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, uric acid, and triglyceride levels, and high urinary amylase concentration. Glucosuria was related to high serum glutamic-oxaloacetic transaminase concentration and a history of gastrectomy. Hematuria was related to high age and high urinary amylase levels. By chi-square test, there was a significant correlation between proteinuria and hematuria (p < 0.001) and between hematuria and glucosuria (p < 0.001), but no correlation was found between proteinuria and glucosuria. The incidence of diabetes mellitus was 10.8% (25 out of 231 patients), but transient hyperglycemia was observed in some patients without diabetes mellitus on admission. Elevated hemoglobin A1, hemoglobin A1c, and fructosamine concentrations were observed in patients with either impaired glucose tolerance or transient hyperglycemia, which suggested the presence of persistent hyperglycemia before admission. On discharge, only 12 out of 198 patients (6.1%) showed abnormal urinalysis. We report that heavy ethanol consumption induces transient abnormal urinalysis results in Japanese alcoholics.

Antibody response to islet antigens in anti-CD4/prednisolone immune intervention of type 1 diabetes

Cytoplasmic islet cell antibodies, glutamic acid decarboxylase autoantibodies, spontaneous insulin autoantibodies, and insulin-induced antibodies were analyzed in a 1-year follow-up study of 12 newly diagnosed patients with insulin-dependent diabetes mellitus aged 14 +/- 2 years (range 7-20 years) who had been initially treated with either multiple injections of insulin alone (control group) or, in addition, anti-CD4 monoclonal antibody/prednisolone (treatment group). Despite individual variations in islet cell antibody titers, there were no significant differences in the prevalence or changes in the mean titers between the two groups. Glutamic acid decarboxylase autoantibodies remained almost unchanged, but correlated with levels of islet cell antibodies. While at initiation of treatment only 50% of the patients from both groups had spontaneous insulin autoantibodies, all patients developed insulin-induced antibodies upon conventional insulin therapy during the course of follow-up. This was not related to islet cell antibody or glutamic acid decarboxylase antibody levels. The insulin requirement was markedly reduced through the period of follow-up, but did not significantly differ between the two groups. A correlation between islet cell antibody levels and insulin requirement was observed in the control group but not in the treatment group. Plasma levels of the antibodies were not associated with changes in stimulated C-peptide or hemoglobin A1 concentrations. Activated T-lymphocytes persisted in both groups of patients, but their mean levels were not significantly different. The reason for the absence of statistically significant differences between treatment and control groups could be due to the small number of patients in the study. In conclusion, short-term immune intervention with anti-CD4 monoclonal antibody in addition to insulin therapy did not suppress autoimmune reactions towards the beta cells.

Targets set reference points for clinic comparisons

EDITOR,--Chris Butler and colleagues show impressively how systematic collection and use of case based information can help identify problems in the search for improved quality of care in diabetes.1 Pointing to the difficulties with setting targets in the treatment of diabetes and in its care, they argue that targets for haemoglobin A1 concentration may be set more on an idealistic than on a realistic basis. They also argue that inappropriate targets, in many instances, may do more damage than good to the ultimate goal of reducing morbidity and mortality through improved metabolic control. A central question about setting targets is whether they should be “visionary” or attainable by a certain proportion of the people concerned. On …

Lesson of the Week: Insulin dependent diabetes in nonagenarians

The National Diabetes Data Group's definition of insulin dependent diabetes misleadingly talks of “predominant onset in youth.”1 Over 40 years ago Lawrence wrote that many diabetic patients aged over 70 were insulin deficient.2 It has recently been shown in Denmark that the annual incidence of insulin dependent diabetes after the age of 30 is 8.2 per 100 000 and is remarkably constant from the fourth to the ninth decade; thus at least 44% of all cases are diagnosed after the age of 30.3 We report on two patients who developed insulin dependent diabetes at the ages of 88 and 93. ### CASE 1 An 88 year old woman presented with a five month history of lethargy, weight loss, and nocturia. She was found to be hypothyroid, with a high titre of thyroid autoantibodies. One of her seven siblings had developed diabetes of uncertain type at the age of 75 and a granddaughter had Graves' disease. A month later she became thirsty, was found to have diabetes, and was treated with glibenclamide 5 mg twice daily by her general practitioner. She was referred to us three months later with a random blood glucose concentration of 15.1 mmol/l and a haemoglobin A1 concentration of 11.6% (normal range 5.0%-7.5%). Apart from bilateral cataracts there were no diabetic complications, but she had a body mass index of 23 kg/m2 and was …

Nephroprotective effects of nitrendipine in hypertensive type I and type II diabetic patients.

Hypertension is significantly involved in the progression of diabetic nephropathy and in the development of end stage renal disease in both type I and type II diabetes mellitus. We have investigated whether long-term monotherapy with a calcium antagonist, nitrendipine, prevents the development of overt diabetic nephropathy in type I and type II diabetic patients with mild to moderate hypertension and persistent microalbuminuria (ie, incipient nephropathy). After a 4-week run-in and washout period, respectively, 25 patients met the inclusion criteria. Twenty-two patients (six with type I and 16 with type II diabetes) completed the 12-month study. Twelve months of treatment with nitrendipine resulted in a significant reduction in systolic blood pressure in patients with type I (157.5 +/- 8.1 mm Hg v 135.8 +/- 4.2 mm Hg, P < 0.05) and type II (163.1 +/- 4.3 mm Hg v 135.9 +/- 3.6 mm Hg, P < 0.001) diabetes. A significant reduction also was seen in diastolic blood pressure (91.7 +/- 1.7 mm Hg v 79.2 +/- 3.5 mm Hg in type I diabetic patients, P < 0.01; 94.7 +/- 1.4 mm Hg v 78.1 +/- 1.5 mm Hg in type II diabetic patients, P < 0.001). A significant reduction in albuminuria was associated with the blood pressure reduction in both type I (57.8 +/- 11.9 mg/24 hr v 24.9 +/- 5.9 mg/24 hr, -57%) and type II (134.6 +/- 20.7 mg/24 hr v 70.3 +/- 16.8 mg/24 hr, -48%) diabetic patients. The mean glomerular filtration rate increased by 21% (112 +/- 12 mL/min v 135 +/- 14 mL/min) and by 23% (106 +/- 12 mL/min v 130 +/- 14 mL/min) in type I and type II diabetic patients, respectively. No significant changes were found in renal plasma flow rates or in serum concentrations of beta 2-microglobulin. With the exception of a significant (P < 0.05) reduction in hemoglobin A1 concentration in type II diabetic patients after 3 months of treatment with nitrendipine, fasting blood glucose, hemoglobin A1, residual beta-cell function (C-peptide levels), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and body mass index remained essentially unchanged during follow-up. These findings suggest that 12 months of monotherapy with the dihydropyridine-type calcium antagonist nitrendipine reduced albuminuria and increased the lowered glomerular filtration rate without adverse effects on glucose and lipid control.(ABSTRACT TRUNCATED AT 400 WORDS)

Course of brittle diabetes: 12 year follow up.

To determine the course of brittle diabetes. 12 year follow up of patients identified in 1977-9 as having brittle diabetes; retrospective review of the case notes. Nottingham health district. 25 brittle diabetic patients were identified in 1979-9; 11 (five men) had three or more admissions with ketoacidosis between June 1977 and 1979 and 14 (eight men) had three or more attendances at the accident and emergency department with hypoglycaemia in 1978. Two controls from our diabetic register were matched to each patient for age, sex, and duration of diabetes. Frequency of ketoacidosis and severe hypoglycaemia in the 12 years after ascertainment; diabetic control and complications in 1988-90; retrospective attribution of the cause of brittleness. Patients with recurrent ketoacidosis had had a median (range) of 28 (8-67) episodes. One man died of a cerebral tumour but five of the surviving nine patients had not been admitted in the past two years, although diabetic control remained poor (median haemoglobin A1 concentration 14%). Seven patients had pure hypoglycaemic brittleness, and five had also had eight or more admissions with ketoacidosis (mixed brittleness). Two died of uraemia within a year after ascertainment and two others in hypoglycaemic coma seven and 12 years later. Brittle diabetes was in most cases related to a specific situation, usually unhappiness at home or school. Brittle diabetes is often episodic and almost always related to stressful life circumstances. Once the underlying cause is removed it tends to improve. Recurrent hypoglycaemic brittleness of psychological origin has a poor prognosis.

Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors for stroke in the Chinese.

We analyzed the serum concentrations of lipids and lipoproteins and the prevalence of other risk factors in a case-control study of 304 consecutive Chinese patients with acute stroke (classified as cerebral infarction, lacunar infarction, or intracerebral hemorrhage) and 304 age- and sex-matched controls. For all strokes we identified the following risk factors: a history of ischemic heart disease, diabetes mellitus, or hypertension; the presence of atrial fibrillation or left ventricular hypertrophy; a glycosylated hemoglobin A1 concentration of greater than 9.1%; a fasting plasma glucose concentration 3 months after stroke of greater than 6.0 mmol/l; a serum triglyceride concentration 3 months after stroke of greater than 2.1 mmol/l; and a serum lipoprotein(a) concentration of greater than 29.2 mg/dl. We found the following protective factors: a serum high density lipoprotein-cholesterol concentration of greater than 1.59 mmol/l and a serum apolipoprotein A-I concentration of greater than or equal to 106 mg/dl. The patterns of risk factors differed among the three stroke subtypes. When significant risk factors were entered into a multiple logistic regression model, we found a history of hypertension, a high serum lipoprotein(a) concentration, and a low apolipoprotein A-I concentration to be independent risk factors for all strokes. The attributable risk for hypertension was estimated to be 24% in patients aged greater than or equal to 60 years. In this population, in which cerebrovascular diseases are the third commonest cause of mortality, identification of risk factors will allow further studies in risk factor modification for the prevention of stroke.

A Randomized Study of SMS 201–995VersusBromocriptine Treatment in Acromegaly: Clinical and Biochemical Effects

Twenty-six acromegalic patients were randomized to treatment with either SMS 201-995 or bromocriptine in increasing doses and were investigated before treatment, after 2, 4, and 8 weeks of treatment, and 2 weeks after discontinuation of treatment. There were two dropouts from the bromocriptine group and one from the SMS 201-995 group. Amelioration of clinical signs and symptoms was seen in both groups during treatment. After 8 weeks mean 12-h GH concentrations had declined from 13.8 +/- 5.2 to 2.9 +/- 4.4 (mean +/- SEM) in SMS 201-995-treated and from 18.8 +/- 7.5 to 5.4 +/- 1.2 micrograms/L in bromocriptine-treated patients. Somatomedin-C concentrations fell from 3.04 +/- 0.36 to 1.43 +/- 0.36 in SMS 201-995-treated and from 2.93 +/- 0.40 to 2.13 +/- 0.27 U/mL in bromocriptine-treated patients. Size reduction of the pituitary tumor was seen in one patient receiving bromocriptine. Gastrointestinal glucose absorption was delayed, and insulin secretion suppressed during treatment with SMS 201-995. Hemoglobin-A1 concentrations remained unchanged in SMS 201-995-treated patients, but declined in the bromocriptine group. Side-effects were common, but usually tolerable, with both treatments. It is concluded that both drugs are of benefit in the treatment of acromegaly.

Association between diabetes, severe hypoglycaemia, and electroencephalographic abnormalities.

Serial electroencephalographic recordings were made in 70 diabetic children and findings were related to age at electroencephalography and at diagnosis, duration of diabetes, daily insulin dose, long term metabolic control assessed by glycated haemoglobin A1 (HbA1) concentrations, and severe hypoglycaemic episodes. Abnormalities were found in 18 (26%) of diabetic children, and in only five (7%) of control subjects. There were no associations between electroencephalographic abnormalities and duration of diabetes, daily insulin dose, or HbA1 concentration. Diabetic children with electroencephalographic abnormalities were younger, had an earlier onset of diabetes and 21/34 (62%) of them had previously severe attacks of hypoglycaemia, whereas abnormalities were found in only 13/43 (30%) of diabetic children who had not had severe hypoglycaemia. All diabetic children with hypoglycaemic convulsions had permanent electroencephalographic abnormalities. The degree of metabolic control had no effect on the electroencephalographic findings during the early years of diabetes, but previous severe hypoglycaemia, young age, and early onset seem to be important risk factors for electroencephalographic abnormalities.

Insulin autoantibodies at the clinical manifestation of Type 1 (insulin-dependent) diabetes ? a poor predictor of clinical course and antibody response to exogenous insulin

To study the possible clinical significance of the appearance of insulin autoantibodies prior to the diagnosis of Type 1 (insulin-dependent) diabetes, and their value in predicting the antibody response to exogenous insulin, we observed 46 newly diagnosed diabetic children and adolescents over the year following diagnosis for the occurrence and duration of clinical remission, daily insulin dose, metabolic control, residual B-cell function, insulin-binding antibodies and conventional as well as complement-fixing islet cell antibodies. Insulin-binding antibodies were determined using both monoiodinated human and porcine insulin. Sixteen children (34.7%) were positive for insulin autoantibodies upon diagnosis of Type 1 diabetes. These subjects were significantly younger (6.2 +/- 1.0 versus 10.8 +/- 0.8 years; mean +/- SEM, p less than 0.001), and their haemoglobin A1 levels were lower (14.1 +/- 0.6 versus 16.0 +/- 0.8%, p less than 0.05) at diagnosis than in the insulin autoantibody negative group. There were no significant differences in the occurrence and duration of clinical remission between insulin autoantibody-positive and -negative test groups. Daily insulin dose, haemoglobin A1 and serum C-peptide concentrations were of the same magnitude in both groups after the diagnosis, and no association could be found between the presence of insulin autoantibodies at diagnosis and persistently positive islet cell antibodies. In tests conducted 3 months after diagnosis, the group of patients with insulin autoantibodies showed significantly higher levels (p less than 0.05) of antibodies binding human insulin than the group negative for insulin autoantibodies, but no significant differences could be found between the insulin binding titres of the two groups in subsequent analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Microalbuminuria in non-insulin-dependent diabetes: its prevalence in Indian compared with Europid patients.

Non-insulin-dependent diabetes mellitus is strikingly common in British Indians, but their susceptibility to diabetic complications is unknown. The ratio of albumin to creatinine concentrations was measured in samples of the first urine voided in the morning in 154 Indian and 82 Europid patients with non-insulin-dependent diabetes and in a control group of 129 non-diabetic Indians. The ratio was significantly higher in the Indian patients than in the Europid patients and the Indian controls. There were no significant correlations between the logarithm of the albumin: creatinine ratio and age, known duration of diabetes, haemoglobin A1 concentration, or body mass index within either diabetic group. Hypertension and raised albumin:creatinine ratio were significantly associated, and significant correlations were seen between the logarithm of the albumin:creatinine ratio and systolic and diastolic blood pressures in the Indian but not the Europid diabetics. Because of the high prevalence of diabetes at a relatively early age in Indians, nephropathy may emerge as an important clinical problem.

HLA-antigens and immunity to insulin in insulin-dependent diabetics with or without diabetic neuropathy.

In order to define genetic, immunological and metabolic risk factors and markers associated with diabetic neuropathy (DN) 47 insulin-dependent diabetic patients with neuropathy were compared to 30 age-matched insulin-dependent diabetes mellitus (IDDM) patients without neuropathy. Patients with diabetic neuropathy more often had proliferative retinopathy and Albustix positive proteinuria than patients without neuropathy. Judged by haemoglobin A1 (HbA1) concentrations measured during the preceding two years glycaemic control was worse in patients with than without diabetic neuropathy. The frequency of HLA-antigens DR3, DR4, DR3/DR4, B8, and B15 were increased and those of DR2 and B7 decreased in the diabetic patients. The frequency of any of these HLA-antigens did not differ in patients with or without diabetic neuropathy. There were no significant differences in the frequencies of insulin antibodies or proliferative responses to insulin antigens between patients with or without diabetic neuropathy. However, patients who were HLA-DR3/DR4 heterozygotes and had diabetic neuropathy responded to insulin antigens more often by proliferation than DR3/DR4 positive patients without diabetic neuropathy. Thus poor glycaemic control is associated with an increased risk for diabetic neuropathy. Patients with DR3/DR4 heterozygocity and failing to respond to insulin antigens by proliferation seem to be less prone to develop diabetic neuropathy.

Postprandial walking exercise in pregnant insulin-dependent (type I) diabetic women: Reduction of plasma lipid levels but absence of a significant effect on glycemic control

In this study 42 pregnant women with type I diabetes and 28 nondiabetic controls were recruited to participate in a postprandial walking exercise program. Exercise patients were instructed to walk 20 minutes (1 mile) after each meal and were divided into two groups: group 1 were normal nondiabetic controls and group 2 were women with type I diabetes. There were two nonexercise comparison groups: group 3, nondiabetic controls, and group 4, women with type I diabetes. Diabetic women were followed weekly in an intensive perinatal program. Glycemic control was assessed by serial hemoglobin A1 concentration measurements, home blood glucose monitoring, 24-hour glucose profiles, and 24-hour quantitative urinary glucose loss. Glycemic control was modestly but not significantly superior in the diabetic exercise group 2 compared with the diabetic nonexercise group 4. Exercise was associated with lower fasting cholesterol and triglyceride values in both controls and diabetic women, with significantly lower fasting plasma triglyceride levels in the diabetic exercise group (p less than 0.02). There were no adverse effects of postprandial walking exercise in mothers or infants.

Three year prospective study of visual function and retinopathy in diabetics with improved glycaemic control

The visual function and degree of retinopathy was assessed, over a three-year period, in a cohort study of twenty-eight diabetics, in whom glycaemic control was improved by intensive monitoring and supervision of conventional therapies. With the exception of visual acuity and some tests of visual field sensitivity, there was no significant change in visual functions or retinopathy; with improved control of blood glucose, these two visual functions showed a small initial deterioration and subsequently returned towards starting values. Six subjects required laser photocoagulation for progressive peripheral neovascularisation (including two subjects with peripheral new vessels), the six having a significantly longer duration of diabetes, slightly worse measures of extra-foveal retinal functions and a significantly greater reduction in haemoglobin A1 concentration during the first six months of the study. In this study, the improvement of blood glucose control by intensive supervision of conventional therapy did not appear to be associated with the significant acute deterioration of visual function or retinopathy that has been reported with the strict diabetic control by multiple daily insulin injections or continuous subcutaneous insulin infusion.

Effects of continuous subcutaneous insulin infusion and intensified conventional therapy on peripheral and autonomic nerve dysfunction.

The objective of this study was to determine whether a favorable effect of short term continuous sc insulin infusion (CSII) therapy on the peripheral and autonomic nervous system could be maintained by subsequent intensified conventional treatment (ICT). Nine type I diabetic patients, aged 18-32 yr, who had been diabetic for 4-23 yr and had reduced nerve conduction velocities received CSII for 4 weeks and subsequently ICT for up to 26 weeks. Motor and sensory nerve conduction velocities (MNCV and SNCV) and heart rate variations during deep breathing (E/I ratio), during lying and standing (30/15 ratio), and during the Valsalva maneuver (Valsalva ratio) were measured before CSII and at intervals of 1, 2, 4, 6, 10, and 26 weeks. During CSII, MNCV and SNCV increased significantly (P less than 0.01), the E/I ratio improved in seven patients (P less than 0.05), the Valsalva ratio increased in eight patients (P less than 0.01), and the 30/15 ratio increased in five patients. The E/I ratio increased significantly earlier than the Valsalva ratio (P less than 0.025). During ICT, nerve conduction velocity slightly, though not significantly, decreased, and the results of the cardiovascular reflex tests also gradually declined. The hemoglobin A1 concentration before initiation of CSII and the diminution of the hemoglobin A1 concentration during CSII therapy were inversely correlated to the increase in MNCV (P less than 0.01 and P less than 0.05, respectively). In conclusion, CSII improved peripheral and autonomic nervous system function, but the improvement diminished somewhat during ICT.

Effect of dietary advice on diabetic control

AbstractDiabetic outpatients attending a district hospital had minimal dietary advice before the introduction of a dietetic service in 1982. This offered the opportunity to assess the effect of dietary advice on diabetic control by observing changes in blood haemoglobin A1 (HbA1) concentration. Following dietary advice it was found that 20% of patients had an unchanged HbA1 concentration, 13% had increased HbA1 concentration, whilst 67% had significantly reduced HbA1 concentration.

Glycosylated hemoglobin: a sensitive indicator of gestational diabetes.

Previous studies suggested that the assessment of hemoglobin A1 (HbA1) concentration was a poor indicator of diabetes in pregnancy. However, HbA1 was measured by ion exchange chromatography, which is subject to spurious alterations. To reevaluate the use of glycosylated hemoglobin concentration (GlyHb) as an indicator of gestational diabetes, 64 women at 10 to 15 weeks' gestation were studied by measuring GlyHb by a specific affinity chromatography assay, and blood glucose concentration was determined one hour post a 50-g oral glucose load. Gestational diabetes developed in 15 women in whom GlyHb (7.4 +/- 0.2%) was greater than in normal pregnant women (5.7 +/- 0.1%, P less than .001). If a GlyHb of 6.3% were chosen as the threshold for diagnostic evaluation for diabetes, only 6.7% of the gestational diabetics would have missed diagnosis. Of normal women, 14.2% would have been subjected to glucose tolerance test. GlyHb elevation was associated with the birth of infants large for gestational age. The assessment of GlyHb by affinity chromatography between 10 and 15 weeks' gestation may be a sensitive predictor of patients who will develop gestational diabetes.

Neonatal polycythemia in infants of insulin-dependent diabetic mothers.

The rate of neonatal polycythemia was determined prospectively in 34 infants of diabetic mothers pair-matched to 34 infants of nondiabetic mothers (control group) for site of sampling, time of sampling, time of cord clamping, gestational age, mode of delivery, and one- and five-minute Apgar scores. Polycythemia (venous hematocrit greater than or equal to 65%) was present in 29.4% of infants of diabetic mothers and 5.9% of control subjects (P less than .03). Mean nucleated red blood cell counts were significantly higher in infants of diabetic mothers than in controls. Polycythemia did not correlate with higher maternal hemoglobin A1 concentration or with increased infant weight percentile, but did correlate with neonatal hypoglycemia. The authors speculate that increased erythropoiesis exists in infants of diabetic mothers and might be subsequent to fetal hypoxemia due to fetal hyperglycemia, hyperinsulinism, and hyperketonemia.