Risk factors for frequent and severe hypoglycemia in type 1 diabetes.

OBJECTIVE: To determine the risk of frequent and severe hypoglycemia and the associated demographic and clinical risk factors. RESEARCH DESIGN AND METHODS: Demographic and diabetes self-management factors were measured in 415 subjects followed prospectively for 4-6.5 years of type 1 diabetes duration as participants in a population-based incident cohort. Blood samples were collected up to three times yearly to test glycosylated hemoglobin (GHb) levels. Reports of frequent (2-4 times/week) and severe (lost consciousness) hypoglycemia as well as other diabetes self-management data were collected by questionnaires. RESULTS: Frequent hypoglycemia was common (33 and 35% of participants reported this on the 4- and 6.5-year questionnaires, respectively), whereas severe hypoglycemia occurred much less often. Better glycemic control (odds ratio [OR] 1.3 per 2% decrease in GHb, 95% CI 1.1-1.5) and more frequent self-monitored blood glucose (1.5 per blood glucose check, 1.3-1.7) were independently related to frequent hypoglycemia. The association of frequent hypoglycemia with intensive insulin therapy increased with age. Better glycemic control (1.5 per 2% decrease in GHb, 1.2-2.0) and older age were related to severe hypoglycemic reactions. No sociodemographic factors other than age increased the risk of hypoglycemia. CONCLUSIONS: Frequent hypoglycemia was common in a population representing the full range of glycemic control in the community. Intensive insulin management and blood glucose monitoring independently predicted frequent but not severe hypoglycemia. This information may be useful for updating patients such that minor changes in diabetes management might decrease the daily burden of this condition while maintaining intensive insulin therapy.

Differentiation of acute cortical and subcortical ischemic stroke by risk factors and clinical examination findings.

BACKGROUND: Differentiation between acute cortical and subcortical ischemic stroke may be problematic when cortical stroke presents without obvious cortical deficits such as aphasia, neglect or hemianopia. This study explores stroke risk factors and clinical variables that may assist in this differentiation. METHODS: Records of consecutive patients with acute ischemic stroke, examined within 72 h of symptom onset, were reviewed. Stroke type was verified by clinical course and follow-up imaging. Stroke risk factors and acute examination findings were compared by odds ratios and positive predictive values for cortical and subcortical stroke. RESULTS: For 355 patients studied, 237 had cortical stroke and 118 had subcortical stroke. Odds ratios for cortical stroke were highest for atrial fibrillation by EKG (OR = 4.77, CI = 2.08-10.94), recent hospitalization (OR = 4.51, CI = 2.39-8.53) and nonalert mental status (OR = 4.50, CI = 2.29-8.87). Possible cardioembolic condition, ischemic heart disease and peripheral vascular disease were also significant, but hypertension, age and diabetes mellitus were not significantly different for the stroke subtypes. Cortical deficits were absent in 19.4% of cortical stroke patients on initial examination. Predictive models were generated based on the presence or absence of cortical deficits and the interaction of significant risk factors with degree of motor deficit. CONCLUSIONS: There are clinical features that, in addition to initial examination, may help differentiate cortical from subcortical ischemic stroke. These features may be relevant to both diagnostic and therapeutic approaches to acute stroke.

Incidence of retinopathy and associated risk factors from time of diagnosis of insulin-dependent diabetes.

OBJECTIVE: To describe the prevalence at baseline and 4-year incidence of retinopathy and its relation to glycemic control from the time of diagnosis of insulin-dependent diabetes. DESIGN: Geographically defined population-based study. SETTING: Twenty-eight-county area in Wisconsin. STUDY POPULATION: Incipient cohort of children, teenagers, and young adults (n = 354) up to 30 years of age with newly diagnosed insulin-dependent diabetes. MAIN OUTCOME MEASURE: Diabetic retinopathy as determined by gradings from 30 degrees color stereoscopic photographs of the Diabetic Retinopathy Study 7 standard fields. RESULTS: The prevalence of retinopathy at diagnosis was 1.3%. Four years after diagnosis of diabetes, retinopathy was first identified in 5.1% of our cohort and in 9.7% of those 15 years of age or older. After controlling for age, subjects with a mean glycosylated hemoglobin level of 12% or greater were 3.2 times as likely (95% confidence interval, 1.1-9.9) to have retinopathy present at follow-up as were subjects with a mean glycosylated hemoglobin level of less than 12%. CONCLUSION: Population-based data on the frequency and incidence of retinopathy from the time of diagnosis of insulin-dependent diabetes mellitus provided by this study suggest a possible reduction in risk of developing retinopathy in those in whom glycemic control is achieved from the time of diagnosis.

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.

A case-control study of group B Coxsackievirus immunoglobulin M antibody prevalence and HLA-DR antigens in newly diagnosed cases of insulin-dependent diabetes mellitus.

From July 1984 through June 1987, we sought referral of all newly diagnosed cases of insulin-dependent diabetes mellitus aged 0-29 years in a 14-county area of southern Wisconsin. Each case was asked to identify an age- and sex-matched friend control. Blood specimens were obtained for group B Coxsackievirus immunoglobulin M (IgM) neutralizing antibody titer on cases and controls and HLA-DR typing of cases. There were 225 cases referred, of whom 194 participated. Of these, 134 had both HLA-DR typing and an initial serum specimen drawn within 59 days of diagnosis. Only two of 50 insulin-dependent diabetes mellitus cases less than age 9 years had positive (greater than or equal to 1:16) group B Coxsackievirus IgM titers. Fifteen of 84 cases aged 10-29 years (17.8%) were group B Coxsackievirus IgM positive, compared with five of 71 controls (7.0%). However, group B Coxsackievirus IgM antibody positivity was concentrated in HLA-DR3-positive cases (10 of 39, odds ratio = 4.55, 95% confidence interval 1.26-18.27, p less than 0.01). HLA-DR3-negative cases were not different from controls in group B Coxsackievirus IgM prevalence. Eighty-three percent of the cases and 86% of the group B Coxsackievirus IgM-positive cases were referred in the first 24 months of study. These data demonstrate an association between group B Coxsackievirus infections and onset of insulin-dependent diabetes mellitus only in HLA-DR3-positive persons aged 10 years or older. The data also suggest that diabetogenic group B Coxsackievirus strains may circulate only periodically; however, a longer period of study is needed to examine this possibility.

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.

Risk of diabetes in siblings and other relatives of IDDM subjects.

The risk of insulin-dependent diabetes mellitus (IDDM) was examined in siblings of an unselected population (n = 194) of newly diagnosed diabetic individuals less than 30 yr old. From 1 July 1984 to 30 June 1987, diabetic subjects (proband) identified within a geographically defined area of southern Wisconsin were studied. IDDM occurred among siblings of probands in 13.5% of families and was associated with proband age at diagnosis. The highest risk was found for diabetic subjects less than 10 yr old at diagnosis (P = 0.04). We did not find an association between sibling IDDM and proband sex, HLA-DR3/4, duration of symptoms, or ketosis at diagnosis. In addition, the odds ratio (OR) for the association of IDDM in the proband with IDDM in parents and second- and third-degree family members was examined by case-control methodology. Diabetic subjects were matched to two types of control subjects (friends and general population) by age stratum and sex. The OR for IDDM was not increased significantly if parental IDDM or non-insulin-dependent diabetes mellitus (NIDDM) was reported. However, there were very few parents with diabetes among diabetic or control subjects. In 6.4% of diabetic subjects, one parent had IDDM, 54% of whom were fathers. In 4.3% of diabetic subjects, one parent had NIDDM, and 57.1% of these were fathers. The OR for IDDM was significantly increased if second- and/or third-degree relatives had IDDM (OR diabetic subjects vs. general population 2.33 [P less than 0.05)] or NIDDM (OR diabetic subjects vs. friends 2.05 [P less than 0.01]).(ABSTRACT TRUNCATED AT 250 WORDS)

SIDS: race as a factor.

In Wisconsin, the rate of postneonatal deaths attributed to sudden infant death syndrome (SIDS) for the period 1978-1987 was 6.7 per 1,000 live births for Native Americans, 3.6 for blacks, and 1.4 for whites. To investigate racial differences in case ascertainment and risk for SIDS mortality, this study used matched birth-death certificate data for the 1,111 reported SIDS deaths during the 10-year period. At least 90% of all SIDS deaths occurred before 6 months of age; seasonal variation in time of death and autopsy rates were similar by race. The reported higher risk of SIDS for male infants and those with low birth weights did not occur among Native Americans. Low birth weight was a stronger risk for SIDS among whites than blacks. Our findings suggest that diagnostic practices may not account for racial differences in SIDS mortality. Patterns of risk, however, appear to vary by race.

Cross-sectional study of recurrent herpes labialis. Prevalence and risk factors.

Consecutive blood donors at 25 sites in southern Wisconsin were interviewed in 1985 to ascertain recurrent herpes labialis histories, other perioral conditions, and status on possible predisposing factors and correlates of lesion recurrence. The prevalence of recurrent herpes labialis was 32.9%. Of the cases, 51.3% reported at least two recurrences per year, 8.6% characterized their condition as severe, and 10% sought medical care. Relations were examined between recurrent herpes labialis and family history of the disease, ethnicity, complexion, hair and eye color, other chronic perioral conditions, solar radiation, exposure to dental procedures, and smoking. The risk of recurrent herpes labialis associated with disease in various first-degree family members, estimated by age-adjusted odds ratios (nominal 95% confidence intervals) were: mother, 3.30 (1.86-5.84); father, 3.80 (1.80-8.12); sister(s), 3.93 (2.25-6.89); and brother(s), 6.81 (3.14-15.04). Ethnicity and phenotypes were not related to disease status. Cases had a higher prevalence of recurrent aphthous ulcers (odds ratio = 3.00, 95% confidence interval = 1.79-5.02) and reported more exposure to solar radiation and more extensive dental histories.

Incidence and differences in urban-rural seasonal variation of type 1 (insulin-dependent) diabetes in Wisconsin.

In a hospital-based records study of Type 1 (insulin-dependent) diabetes mellitus among persons aged 0 to 29 years in two Wisconsin, USA counties (1970-79), the age-adjusted yearly incidence rate for white males (16.4/100,000) was significantly higher than for white females (11.6/100,000) (p = 0.006). Overall age-adjusted rates are similar to rates previously reported for the United States and the northern European countries of Denmark and Norway. Seasonal variation in diagnosis was found for total cases and males aged 10 to 19 years. A striking difference also was found in seasonal diagnosis between urban and rural cases. A diagnosis peak in the third and fourth quarter among rural cases contrasted with even quarterly distribution among urban cases. In addition, 52% of rural male cases aged 10 to 19 years were diagnosed during the fourth quarter while no seasonal pattern occurred among urban males the same ages. These findings identify subgroups for focus of future etiologic investigations.

Hepatitis B in Wisconsin male prisoners: considerations for serologic screening and vaccination.

To develop a protocol for prevention of hepatitis B virus (HBV) transmission in Wisconsin prisons, we interviewed 619 male prisoners at incarceration to obtain information on hepatitis B risk factors. We defined previous infections by the presence of hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs), or antibody to hepatitis B core antigen (anti-HBc). Logistic regression was used to develop a model of relative risk (RR) of HBV infection. Use of illicit intravenous (IV) drugs was the most important risk factor because of a high prevalence of IV drug use and an RR which ranged from 2.93-7.47. Other important risk factors were: prior hepatitis or jaundice (RR = 6.28), race (RR = 2.54 for Blacks, RR = 3.28 for Latinos), transfusion (RR = 3.00), and age. Previous imprisonment was not an independent risk factor for HBV, hence selective serologic screening and vaccination of prisoners are justified rather than mass screening and vaccination. Based upon prevalence of hepatitis B markers in subgroups, it is necessary to screen prisoners with prior hepatitis or jaundice, prior transfusion, and users of IV drugs. The identification of HBsAg carriers by such screening could prevent infection of "household" contacts. Users of IV drugs who are susceptible to HBV infection should be vaccinated. The remaining prisoners constitute a low-risk group for HBV infection and do not require serologic screening or vaccination.

Short-duration exposure and the transmission of rhinoviral colds.

Transmission of infection with rhinovirus type 55 was attempted under natural circumstances of interaction among 26 experimentally infected donors and 33 antibody-free (titer, less than 1:3) recipients. In a total of three experiments, only two recipients (6%) became infected. In the first experiment no transmissions from five donors to nine recipients occurred after 2-3 hr of loud vocalization and card playing in a small room. In the second experiment a cold was transmitted to one (9%) of 11 recipients living in dormitory rooms for 36 hr in groups consisting chiefly of two donors and two recipients. In the third experiment one (8%) of 13 recipients was infected after kissing an infected donor. In studies with rhinovirus type 16, the 50% human infectious dose was found to be 0.28 TCID50 (50% tissue culture infectious dose) in the nose, 2,260 TCID50 on the tongue, and 11,000 TCID50 on the external nares. Rhinoviral infections are difficult to transmit by short-term natural exposure, perhaps because the agent must be present in overwhelming numbers to reach susceptible mucosal cells.

Human infective dose determinations for oral poliovirus type 1 vaccine in infants.

The 50, 10, and 1% human infective doses of poliovirus type 1 vaccine administered orally to 32 infants were estimated to be 72, 39, and 20 tissue culture infective doses, respectively.

Counterimmunoelectrophoresis test for immunoglobulin M antibodies to group B coxsackievirus.

A counterimmunoelectrophoresis test was developed for immunoglobulin M (IgM) antibodies to group B coxsackievirus (CB) types 1 through 5. The IgM precipitin line could be identified and differentiated from the IgG line by treating sera with 2-mercaptoethanol. Antigen purity was demonstrated by single precipitin lines occurring only to the homologous antigen when tested with type-specific hyperimmune rabbit sera. Serum pairs from 19 of 22 patients with documented CB type 1,3,4, and 5 infections were positive for IgM antibody to the infecting serotype, whereas 2 of 7 pairs from CB type 2 patients were positive. Heterologous IgM antibodies were present in sera from 14 fo 29 CB patients. Of the 14 patients with heterologous IgM antibodies, 12 also had greater than or equal to 4-fold rises in whole serum neutralizing antibody to heterologous serotypes. Only three control sera from 72 patients with coxsackievirus group A, echovirus, or other viral infections had IgM antibody to CB serotypes.

Transmission of experimental rhinovirus colds in volunteer married couples.

Communicability of rhinovirus type 16 or type 55 was studied in 24 childless couples; on partner (the donor) was infected with laboratory-grown virus. Initially, both partners lacked antibody to the challenge agent. Rates of transmission between partners were 41% and 33% for type 16 and type 55, respectively. These rates are similar to those determined in epidemiologic studies of natural rhinovirus infection. Although the mucosa of the anterior nares was shown to be highly susceptible to infection (less than one 50% tissue culture infective dose [TCID50]), transmission rarely occurred unless (1) at least 1,000 TCID50 of virus was recovered from the donor's nasal washing, (2) the donor had virus on his hands and anterior nares, (3) he was at least moderately symptomatic, and (4) he spent many hours with his spouse. Since person-to-person transfer of rhinovirus was so dependent upon time spent together and shedding of large amounts of virus by the donor, it seems possible that the chain of infection could be interrupted by environmental manipulation.