Factors associated with avoidance of severe complications after 25 yr of IDDM. Pittsburgh Epidemiology of Diabetes Complications Study I

To identify characteristics associated with long-term avoidance of insulin-dependent diabetes mellitus (IDDM) complications, subjects taking part in an epidemiologic natural history study of childhood-onset IDDM, with a duration of disease greater than or equal to 25 yr, were studied. Nineteen percent of 175 subjects had avoided overt nephropathy, definite cardiovascular and peripheral vascular disease, clinical neuropathy, and proliferative retinopathy. Approximately half of the nonrenal complications occurred in the absence of renal disease. Subjects free of these advanced complications were characterized by a longer duration of disease (P less than 0.05), better lipid profile and blood pressure (P less than 0.01), and considerably lower glycosylated hemoglobin levels (P less than 0.001). Health-related behaviors, including recent medical contact, regular glucose monitoring, physical activity in youth, and avoidance of cigarette smoking, did not relate to complication status, although regular (at least weekly) alcohol consumption was more prevalent (P less than 0.05) in those without complications. We conclude that a lower mean glycosylated hemoglobin level is strongly related to the avoidance of all IDDM complications.     

Psychosocial factors and complications of IDDM. The Pittsburgh Epidemiology of Diabetes Complications Study. VIII.

OBJECTIVE--To investigate whether psychosocial factors are associated with diabetic complications. RESEARCH DESIGN AND METHODS--Questionnaires on quality of life, depressive symptomatology, and personality type were completed and a clinical assessment was performed. The study population was an incident cohort of childhood-onset insulin-dependent diabetic (IDDM) subjects whose duration of IDDM was greater than or equal to 25 yr (n = 175). RESULTS--Patients with macrovascular disease (P less than 0.01) or nephropathy (P less than 0.05) reported significantly poorer quality of life compared with those who were free from all complications. Patients with macrovascular disease also reported greater depressive symptomatology (P less than 0.05). Quality of life significantly deteriorated according to the presence of multiple (greater than or equal to 4) complications (P less than 0.001). Higher depression symptom scores were also related to the presence of greater than or equal to 4 complications (P less than 0.001). Those with multiple complications reported less type A behavior than those without any complications (P less than 0.05). CONCLUSIONS--This study shows that psychosocial differences exist according to both the number and the type of diabetic complications present. Because poorer quality of life and symptoms of depression may both result form complications, prospective follow-up is needed to clarify their temporal interrelationships, and to determine whether type A personality affords any protection against complications or is diminished as a result of developing complications.     

Clinic attendance and glycemic control. Study of contrasting groups of patients with IDDM

OBJECTIVE: To assess factors associated with attendance at a specialized clinic for diabetes care. RESEARCH DESIGN AND METHODS: Adults with insulin-dependent diabetes mellitus (IDDM) in poor (HbA1 greater than or equal to 12%) versus good (HbA1 less than or equal to 10%) control and with no known complications comprised the study group. RESULTS: Infrequent attenders were in worse glycemic control than regular attenders (chi 2 = 6.60, P less than or equal to 0.01) and held health beliefs that downplayed the importance of getting advice from physicians (P less than or equal to 0.002) or providing opinions to physicians about what might be done to improve their health (P less than or equal to 0.001). CONCLUSIONS: Because infrequent attenders are more likely to be in poor glycemic control and thus at greater risk for diabetic complications, engaging them in regularly supervised treatment has important personal and public health implications. Additional studies are needed to understand why some diabetic patients limit their contact with medical providers and to develop more effective strategies for reversing this process. Initial findings from this study suggest that patient beliefs about the doctor-patient relationship may influence clinic attendance.     

Glycemic control in early IDDM. The Wisconsin Diabetes Registry.

OBJECTIVE--A cohort (n = 277) was followed from diabetes diagnosis to evaluate longitudinal glycemic control, urinary C-peptide levels, and certain features of diabetes self-management. RESEARCH DESIGN AND METHODS--Unselected cases with IDDM, who were less than 30 yr of age, were identified at diagnosis from a 28-county area in Wisconsin. Subjects were asked to submit blood every 4 mo for GHb testing, to report aspects of diabetes self-management every 6 mo, and to collect a 24-h urine specimen 4 mo after diagnosis. RESULTS--In the 1st yr of diabetes, the rate of increase (0.23%/mo) in GHb was significant for the cohort (P less than 0.001) and for almost all age and sex subgroups. In the 2nd yr, there was no significant rate of increase for the cohort as a whole (P greater than 0.10). Adolescent males (10-19 yr of age) had a mean GHb level for year 2 higher than males of other age-groups and higher than female adolescents (P less than 0.001). Adolescent males had a significant rate of increase in GHb for year 2 (P = 0.02), unlike all other age and sex subgroups. Adolescents had higher initial 24-h urine C-peptide levels than children less than 10 yr of age (P less than 0.01). During the 2nd yr of diabetes, the percentage of adolescent males reporting three or more insulin injections/day was lower than any other subgroup. CONCLUSIONS--These data-suggest that glycemic control stabilizes during the 2nd yr of IDDM, except in adolescent males, and that this may be due partly to aspects of self-management.     

Natural course of remission in IDDM during 1st yr after diagnosis.

OBJECTIVE--To describe the natural course of clinical remission in insulin-dependent diabetes mellitus (IDDM) when insulin dose is minimized without loss of target glycemia and to identify factors that predict clinical remission. RESEARCH DESIGN AND METHODS--Ninety-five patients, who were placebo-treated control subjects in the Canadian-European multicenter randomized trial of cyclosporin A in recent-onset IDDM, were studied. RESULTS--The mean insulin dose decreased during the first months after diagnosis, with a nadir at 3 mo, when 27% of the patients did not require insulin to maintain target glycemia. At 1 yr, 10% of patients still did not need insulin. Patients not receiving insulin who had glycosylated hemoglobin within the normal range were called remitters. Mean basal and glucagon-stimulated C-peptide values were significantly (P less than 0.025) higher in remitters than nonremitters at the start of the study. Therefore, all patients were divided into those with values above the mean stimulated C-peptide (0.4 nM) and those with values below the mean at entry. The probability of entering a remission with a stimulated C-peptide greater than 0.4 nM was 10 times as high (P less than 0.05) as for those with a stimulated C-peptide below this level. Surprisingly, the beginning and end of the remission were associated with neither major changes in C-peptide levels nor islet cell antibody and insulin-antibody titer. A more rapid loss of stimulated C-peptide occurred in patients who lacked HLA-DR3 and -DR4 (P less than 0.05 at mo 9). CONCLUSIONS--This study shows a higher spontaneous clinical remission rate than expected during the 1st yr after diagnosis. Preserved beta-cell function at entry predicts a greater chance of entering a remission, and a more rapid loss of beta-cell function was seen in patients without HLA-DR3 and -DR4.     

Effect of glycemic control on growth velocity in children with IDDM.

OBJECTIVE--To determine the effect of glycemic control on growth velocity in children with insulin-dependent diabetes mellitus. RESEARCH DESIGN AND METHODS--One hundred twenty-two children with insulin-dependent diabetes mellitus were studied over a 5-yr period. Every 4 mo, glycemic control was assessed by measuring total glycosylated hemoglobin (GHb), pubertal status was determined by physical examination, and height was measured with a stadiometer. Height measurements were normalized for age and sex by converting them to tau scores (the number of SD above or below the mean for age and sex). Alterations in growth velocity were determined by the change in tau scores (delta tau) between visits (i.e., no change in tau score = normal growth velocity; decrease in tau score = growth deceleration; and increase in tau score = growth acceleration). RESULTS--A linear relationship was seen between GHb levels and the change in tau scores (r = -0.117, P = 0.001). GHb values less than 8% were associated with growth acceleration (delta tau = +0.10 +/- 0.03), and the greatest growth deceleration occurred when GHb was greater than 16% (delta tau = -0.07 +/- 0.03). The level of GHb at which growth suppression occurred (mean delta tau became negative) was dependent on pubertal status: Tanner stage 1 greater than or equal to 10%, Tanner stages 2 and 3 greater than or equal to 8%, Tanner stages 4 and 5 greater than or equal to 16%. CONCLUSIONS--Linear growth velocity in children with insulin-dependent diabetes mellitus is heavily related to metabolic control. Children who are prepubertal or in the early stages of puberty are the most vulnerable to growth suppression. Once puberty is well established, growth suppression does not occur until marked hyperglycemia (GHb greater than 16%) exists.     

Glycemic control and peripheral nerve conduction in children and young adults after 5-6 mo of IDDM. Wisconsin Diabetes Registry.

OBJECTIVE--A cohort of people (n = 86) was examined in the first few months after insulin-dependent diabetes mellitus (IDDM) diagnosis to evaluate the effect of hyperglycemia on nerve conduction velocities and latencies. RESEARCH DESIGN AND METHODS--Unselected cases with IDDM, who were 6-29 yr of age, were identified at diagnosis from a large, geographically defined area of southern Wisconsin. Peripheral nerve conduction was measured on a sample from this cohort. RESULTS--Peroneal nerve conduction velocity was significantly inversely related to glycosylated hemoglobin (P less than 0.05, age and height adjusted). All other nerve conduction velocities and latencies (median motor, median sensory, and sural) showed the same tendency, but the associations were not statistically significant. Twenty-four-hour urine C-peptide and duration of diabetes (3-11 mo) were not consistently related to nerve conduction parameters after controlling for age and height. CONCLUSIONS--These findings suggest that as early as 5-6 mo after diabetes diagnosis, and at a time frequently characterized by partial remission of IDDM, hyperglycemia has a role in the acute slowing of nerve conduction velocity. Other factors such as residual endogenous insulin production do not appear to influence these early changes.     

Relationship of skin thickness to duration of diabetes, glycemic control, and diabetic complications in male IDDM patients

Skin thickness is primarily determined by collagen content and is increased in insulin-dependent diabetes mellitus (IDDM). We measured skin thickness in 66 IDDM patients aged 24-38 yr and investigated whether it correlated with long-term glycemic control and the presence of certain diabetic complications. With univariate analysis, skin thickness was increased and significantly related to duration of diabetes (P less than .001), previous glycemic control (P less than .001), retinopathy (P less than .001), cheiroarthropathy (P less than .001), and vibration-perception threshold (P less than .05). There was a negative correlation between forced expiratory volume at 1 s (P less than .05) and vital capacity (P less than .05) with duration of diabetes. Neither skin thickness nor ankle arteriomedial wall calcification correlated with abnormal autonomic function tests. When corrected for duration of diabetes, there was a weak correlation between skin thickness and glycemic control (P less than .05) but no correlation with retinopathy, cheiroarthropathy, and vibration-perception threshold. This study confirms that there are widespread connective tissue changes in diabetes mellitus, although the biochemistry needs further elucidation.     

Colorado IDDM Registry. Incidence and validation of IDDM in children aged 0-17 yr

The purpose of this study was to determine the incidence of insulin-dependent diabetes mellitus (IDDM) among children aged 0-17 yr for age, sex, season, and urban and rural residence of onset in Colorado. Retrospective registration of new-onset cases was conducted from 1978 to 1980, and then prospective registration continued through 1983 with the use of physician reporting with hospital validation. The annual incidence of IDDM was 15.2/100,000 per year (95% confidence interval [CI] 14.1, 16.3), with little difference between the sexes. The highest incidence was in the 10- to 14-yr age-group for both sexes. There was a seasonal peak of winter onset in those aged 10-17 yr, with similar patterns between sex and ethnic groups. No temporal trend over the 6 yr was seen, although an excess of cases was seen for 15- to 17-yr-old boys in 1980-1982. Rates were similar for urban and rural areas of the state. Case ascertainment was estimated to be 93.2% complete (95% CI 91.5, 95.5). Incidence was similar in Colorado to other populations in the United States at similar latitudes. These data serve as a baseline for evaluation of changes in incidence over time, by region, and for the identification of possible outbreaks.     

Infant feeding in Finnish children less than 7 yr of age with newly diagnosed IDDM. Childhood Diabetes in Finland Study Group

OBJECTIVE: We studied associations between the type of feeding in infancy and the incidence of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: We studied 103 newly diagnosed diabetic children less than 7 yr of age and 103 age- and sex-matched population-based control children in a countrywide study. Results: The risk of IDDM was decreased (P less than 0.05) among children breast-fed for at least 7 mo (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.24-0.85) or exclusively breast-fed for at least 3 (OR 0.33, 95% CI 0.13-0.84) or 4 (OR 0.43, 95% CI 0.22-0.84) mo. Also, children who were greater than or equal to 4 mo old at the time of introduction of supplementary milk feeding had a lower risk of diabetes (OR 0.48, 95% CI 0.26-0.91). CONCLUSIONS: The protective effects of a long duration of breast-feeding and a late introduction of dairy products on the risk of IDDM remained significant after adjusting for the mother's education.     

Major malformations in infants of IDDM women. Vasculopathy and early first-trimester poor glycemic control

From animal and in vitro studies, it has been suggested that high environmental glucose, ketone, or insulin concentrations and low glucose or insulin concentrations may be etiologic factors for congenital malformations (CMs) in infants of diabetic mothers (IDMs). Transplacental passage of antibody-bound insulin has been demonstrated in humans. Controversy exists regarding the pathophysiology of CMs in human insulin-dependent diabetes mellitus (IDDM) pregnancies. We hypothesized that CMs in IDMs are associated with maternal vasculopathy, poor first-trimester glycemic control (i.e., hyper- and/or hypoglycemia), advanced White class, and high insulin requirements. We studied 165 first pregnancies of women with IDDM from 1978 to 1986. The goals of glucose control were a fasting blood glucose of less than 100 mg/dl and a 90-min postprandial blood glucose of less than 140 mg/dl. Insulin requirements, body weight, and pre- and postprandial blood glucose were recorded at weekly clinic visits. Maternal blood HbA1 was measured on entry and every 4 wk to confirm that adequate glycemic control was achieved. Women who enrolled in the project were interviewed during gestation by a geneticist/dysmorphologist who obtained genetic and environmental histories using a standard questionnaire. All live-born infants and stillbirths were examined. Each live-born infant was assessed systematically by two independent examiners, a neonatologist and a geneticist/dysmorphologist; examination with standardized checklists was performed in the newborn nursery as soon after birth as was practical. In first pregnancies in the study, there were 13 IDMs with major CMs (7.9%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Decrease of lipoprotein(a) with improved glycemic control in IDDM subjects.

OBJECTIVE: Recently, lipoprotein(a) [Lp(a)] has been identified as a major risk factor for coronary heart disease. There are few data available on the influence of metabolic control on plasma Lp(a) concentrations in subjects with insulin-dependent diabetes mellitus (IDDM), a group at high risk for coronary heart disease. RESEARCH DESIGN AND METHODS: We examined the effects of improved metabolic control on plasma lipid and lipoproteins and Lp(a) concentrations in 12 subjects before and after 21 days of tight metabolic control. RESULTS: Glycosylated hemoglobin declined from 8.4 to 6.9% (P less than 0.001), and Lp(a) declined from 29.7 to 27.1 mg/dl (P = 0.022). There were no significant differences in total, low-density lipoprotein, or high-density lipoprotein cholesterol, although the decline in triglyceride concentrations were borderline statistically significant. The distribution of apolipoprotein(a) isoforms in IDDM patients was not unusual, and the apolipoprotein(a) isoform phenotypes did not change with improved metabolic control. Lp(a) concentrations were also significantly higher than in a population-based control group of nondiabetic subjects from the San Antonio Heart Study. CONCLUSIONS: Although the number of subjects was small and the degree of improvement in metabolic control was modest, the results suggest that improved metabolic control may decrease the risk of coronary heart disease mediated by Lp(a) in IDDM.     

Homogeneity in pattern of decline of beta-cell function in IDDM. Prospective study of 204 consecutive cases followed for 7.4 yr.

OBJECTIVE--To study the natural history of beta-cell function from onset of IDDM to expected deterioration of insulin (C-peptide) secretion and to identify different patterns of decline, if any. RESEARCH DESIGN AND METHODS--A cohort of 204 consecutive newly diagnosed IDDM (clinical criteria) patients were followed prospectively for 7.4 yr (range 6-9 yr), measuring fasting C-peptide at onset, 1, 3, 6, 9, 12, and then every 6 mo until 106 wk (range 104-135 wk). Then, postprandial C-peptide was measured. RESULTS--Fasting C-peptide was 0.17 nM (range 0.11-0.25 nM) at onset followed by an annual increase rate of 0.16 nM/yr (range 0.06-0.48 nM/yr) to a peak of 0.28 nM (range 0.23-0.34 nM/yr) after 25 wk (range 12-39 wk). The subsequent annual decline rate of fasting C-peptide was 0.08 (0.05-0.12) and of postprandial C-peptide 0.03 nM/yr (range 0.02-0.06 nM/yr). None of these parameters showed bimodality in their distribution. However, some parameters were important. In men, fasting C-peptide at onset was lower, but the initial C-peptide increase rate was more pronounced compared to women. Furthermore, insulin-free remission was related to higher C-peptide levels throughout the study. C-peptide was higher during the 1st yr of diabetes in subjects greater than 30 yr of age at onset compared with younger diabetic patients. Stepwise multiple regression analysis showed that age, male sex, and fasting C-peptide at onset were of some predictive value for the C-peptide levels at 5 yr. However, simple group comparisons revealed no significant differences. CONCLUSIONS--No major heterogeneity exists in the pattern of decline of beta-cell function in IDDM, although small differences in pattern could be identified in both sexes, in different age-groups, and in relation to achieving insulin-free remission.     

Psychological characteristics of adults with IDDM. Comparison of patients in poor and good glycemic control

This study was conducted to evaluate selected psychosocial characteristics of contrasting groups of patients with insulin-dependent diabetes mellitus (IDDM), i.e., patients with persistently poor versus good glycemic control. Patients with chronic poor control reported feeling physically best at higher blood glucose levels than patients with good control. They also reported a higher threshold for physical symptoms caused by hyperglycemia without any difference in threshold for hypoglycemic symptoms. No differences between groups were found in level of diabetes knowledge, self-esteem, or psychiatric symptomatology. This study suggests that poorly controlled adult patients have underlying perceptions of hyperglycemic symptoms and physical well-being that distinguish them from patients with well-controlled diabetes. The design of this study does not allow for determination of the causal direction in this relationship. Although these patient reports about glycemic and physical symptoms may be post hoc justifications or unreliable beliefs, they also may be accurate perceptions of physical symptom experiences and therefore could influence their self-care activities with resulting chronic problems in glycemic control. Further research is needed to assess the validity of these observations and their possible role in long-term regulation of glycemia.     

Diabetes mellitus in Alaskan Yup'ik Eskimos and Athabascan Indians after 25 yr.

OBJECTIVE--To estimate the prevalence of diabetes mellitus and overweight in two populations of Alaska Natives and to compare the results with previous data. RESEARCH DESIGN AND METHODS--Participants' heights, weights, and random plasma glucose levels were determined. Those with a glucose of greater than or equal to 6.72 mM received a follow-up glucose-tolerance test, interpreted by WHO criteria. Overweight was defined by National Center for Health Statistics criteria and also by criteria used in previous studies. The subjects were Eskimo and Athabascan residents greater than or equal to 40 yr of age in 15 villages in southwestern Alaska. RESULTS--Diabetes prevalence was 4.7% for Eskimos and 10.0% for Indians. Among Eskimo men and women, the prevalence of overweight was 34 and 56%, respectively, among Indian men and women, it was 29 and 55%, respectively. Comparisons with past data indicate that the prevalence of diabetes has increased from 1.7% in 1962 for Eskimos and 1.8% in 1969 for Indians. CONCLUSIONS--The prevalence of diabetes appears to have increased among Eskimos and Indians in Alaska. Overweight appears to be a significant problem in both groups.     

A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U.K. Prospective Diabetes Study 44)

OBJECTIVE: To determine the degree to which alpha-glucosidase inhibitors, with their unique mode of action primarily reducing postprandial hyperglycemia, offer an additional therapeutic approach in the long-term treatment of type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 1,946 patients (63% men) who were previously enrolled in the U.K. Prospective Diabetes Study (UKPDS). The patients were randomized to acarbose (n = 973), titrating to a maximum dose of 100 mg three times per day, or to matching placebo (n = 973). Mean +/- SD age was 59 +/- 9 years, body weight 84 +/- 17 kg, diabetes duration 7.6 +/- 2.9 years, median (interquartile range) HbA1c 7.9% (6.7-9.5), and fasting plasma glucose (FPG) 8.7 mmol/l (6.8-11.1). Fourteen percent of patients were treated with diet alone, 52% with monotherapy, and 34% with combined therapy. Patients were monitored in UKPDS clinics every 4 months for 3 years. The main outcome measures were HbA1c, FPG, body weight, compliance with study medication, incidence of side effects, and frequency of major clinical events. RESULTS: At 3 years, a lower proportion of patients were taking acarbose compared with placebo (39 vs. 58%, P < 0.0001), the main reasons for noncompliance being flatulence (30 vs. 12%, P < 0.0001) and diarrhea (16 vs. 8%, P < 0.05). Analysis by intention to treat showed that patients allocated to acarbose, compared with placebo, had 0.2% significantly lower median HbA1c at 3 years (P < 0.001). In patients remaining on their allocated therapy, the HbA1c difference at 3 years (309 acarbose, 470 placebo) was 0.5% lower median HbA1c (8.1 vs. 8.6%, P < 0.0001). Acarbose appeared to be equally efficacious when given in addition to diet alone; in addition to monotherapy with a sulfonylurea, metformin, or insulin; or in combination with more complex treatment regimens. No significant differences were seen in FPG, body weight, incidence of hypoglycemia, or frequency of major clinical events. CONCLUSIONS: Acarbose significantly improved glycemic control over 3 years in patients with established type 2 diabetes, irrespective of concomitant therapy for diabetes. Careful titration of acarbose is needed in view of the increased noncompliance rate seen secondary to the known side effects.     

Hyperzincuria in IDDM women. Relationship to measures of glycemic control, renal function, and tissue catabolism

Eighteen women with insulin-dependent diabetes mellitus (IDDM) and 15 nondiabetic women participated in a study of the relationship of zincuria to measures of glycemic control, renal function, and tissue catabolism. In the IDDM women, mean +/- SE glycosylated hemoglobin was 9.8 +/- 0.5%, and fasting plasma glucose was 189 +/- 19 mg/dl; duration of diabetes averaged 15 yr. In comparison with control women, the IDDM women excreted four times as much zinc in the urine. However, the total plasma zinc concentration was significantly higher in the IDDM than in the control women (14.7 vs. 13.4 microM). The increased urinary zinc loss in the IDDM women was not related to urine volume, urinary glucose excretion, fasting plasma glucose concentration, percent glycosylated hemoglobin, or an increased glomerular filtration rate. Total urinary protein losses were four times higher in the IDDM women than in the control women, and these urinary protein losses correlated with the urinary zinc losses (P less than .007). There was no relationship between urinary zinc and the excretion of any of the amino acids, urea, or ammonia. The results of this study show that hyperzincuria in diabetes is not associated with lower plasma zinc levels. An increased zinc absorption, decreased intestinal zinc excretion, or increased tissue catabolism may support higher plasma zinc levels.     

Osteocalcin and Risks of Incident Diabetes and Diabetic Kidney Disease: A 4.6-Year Prospective Cohort Study

OBJECTIVEWe aimed to examine the relationship between osteocalcin (OC) and the risk of incident diabetes and the risk of incident diabetic kidney disease (DKD).RESEARCH DESIGN AND METHODSWe followed 5,396 participants without diabetes (nondiabetes subcohort) and 1,174 participants with diabetes and normal kidney function (diabetes subcohort) at baseline. Logistic regression and modified Poisson regression models were used to estimate the relative risk (RR) of baseline OC levels with incident diabetes and DKD.RESULTSDuring a mean 4.6-year follow-up period, 296 cases of incident diabetes and 184 cases of incident DKD were identified. In the nondiabetes subcohort, higher OC levels were linearly associated with a decreased risk of diabetes (RR for 1-unit increase of log_e-transformed OC 0.51 [95% CI 0.35–0.76]; RR for highest vs. lowest quartile 0.65 [95% CI 0.44–0.95]; P for trend < 0.05). In the diabetes subcohort, OC levels were linearly inversely associated with incident DKD (RR for 1-unit increase of log_e-transformed OC 0.49 [95% CI 0.33–0.74]; RR for highest vs. lowest quartile 0.56 [95% CI 0.38–0.83]; P for trend < 0.05), even independent of baseline estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. No significant interactions between OC and various subgroups on incident diabetes or DKD were observed.CONCLUSIONSLower OC levels were associated with an increased risk of incident diabetes and DKD.