Insulin-dependent Diabetes Mellitus In Population Research Articles

Hospital-Care Utilization and Medical Cost Patterns Among Patients With Insulin-Dependent Diabetes

ObjectiveUsing claims data from an integrated payer–provider, we compared costs incurred by patients with insulin-dependent diabetes mellitus (IDDM) who received Hospital Inpatient/Observation/EmeRgency Department care (HIghER care) for diabetes-related events with those who did not receive such care to identify a target population for interventions in future studies. MethodsA retrospective study pooled real-world claims data for IDDM (type 1 or type 2) between July 1, 2018, and June 30, 2019. Medical claims were used to calculate the total and diabetes-related allowed medical costs to the enterprise and per member per month costs. ResultsMedical and prescription drug coverage from 19 378 members was analyzed. Only 8.4% of the IDDM population received HIghER care but incurred 20% of medical expenses and nearly 40% of diabetes-related medical costs. For HIghER care patients, medical spending was higher in every inpatient and outpatient category (Wilcoxon 2-sample tests, all P < .0001). Non–diabetes-related prescription drug costs were greater in this group (Wilcoxon test, Z = 2.2879, P = .0221), whereas diabetes-related prescription drug costs were higher for non-HIghER care (Wilcoxon test, Z = −9.5918, P < .0001). In a longitudinal study of 29 602 patients over 24 months, previous-year receipt of HIghER care was a significant predictor of HIghER care the subsequent year (odds ratio, 3.28). ConclusionMedical spending for patients receiving HIghER care was disproportionately high and greater in every inpatient and outpatient category. HIghER care receipt the previous year was highly predictive of HIghER care episodes the following year.

Is TAP2*0102 allele involved in insulin-dependent diabetes mellitus (type 1) protection?

In this study, we have investigated the frequencies of TAP1 and TAP2 alleles in a group of 226 persons, living in La Reunion Island, consisting of 70 patients with insulin-dependent diabetes mellitus (IDDM) and most of their first degree relatives ( i.e., 156 parents and full sibling subjects) and previously HLA DQB1, DQA1, and DRB1 genotyped. The population of this island is constituted by a particular structure of highly crossbreeding people. Interestingly, the new TAP2*0104 allele, previously discovered by our team in Reunion Island, was found to be increased in the IDDM population and the calculated HRR was relatively high (HRR = 3.3). This result seems to be due to a positive linkage disequilibrium between TAP2*0104 allele and the highly diabetogenous DQB1* 0201–DQA1* 0501–DRB1 0301 haplotype (HRR = 9), which suggests that TAP2*0104 cannot be considered as an additional predispositional factor, but more as a genetic susceptibility marker of IDDM. In addition, we show that minor alleles (TAP2D, *0102, *0103, *0104) are associated with a restricted number of HLA DQ-DR haplotypes and each of them exhibits a preferential linkage with one particular haplotype. In contrast with other alleles, and despite a HRR value close to 1, we show that TAP2*0102 allele contributes significantly to a drastic reduction of the diabetogenic effect of DQB1*0201–DQA1*0301.1–DRB*0701 haplotype. Indeed, this haplotype, which is usually preferentially transmitted to affected children, is dominantly transmitted to healthy children when it is associated with TAP2*0102. Therefore, this allele seems to contribute to genetic protection to IDDM.

Association of class II HLA antigens and insulin-dependent diabetes mellitus in the population of Vojvodina

Class II HLA antigens were investigated in a group of 28 patients with insulin-dependent diabetes mellitus (IDDM) and 218 healthy unrelated persons (control group) from Vojvodina. We used a modified two-colour immunofluorescence method (serologic technique) to determine the phenotype of DR and DQ locus HlA antigens. Phenotype frequencies of class II HLA antigens were determined in both investigated groups and were used for calculating relative risk (RR). If RR was higher than 1, we calculated the population attributable risk (EF), and if RR was lower than 1, we calculated the preventive fraction (PF). Investigation of statistically significant differences in frequencies of class II HLA antigens in patients and control group was performed by using chi 2 test. Results of investigation showed that values of RR were higher than 1 for HLA DR4 (2,808), DR10 (1,116) and DQ3 (1,386), while we noticed a statistically significant difference in frequencies of HLA DR4 (chi 2 test: 4,805) in patients regarding control group. HLA DQ1 antigen has a preventive role in development of IDDM due to highest value of PF (0,314). Results of our investigation confirm that there is an association of HLA DR4 with IDDM in population of Vojvodina. High values of relative risk of IDDM, noticed in persons with HLA-DR4 antigen, point to the degree of risk of IDDM, which is a disease with great socioeconomic importance in Vojvodina.

Genetic polymorphisms of the renin-angiotensin system and complications of insulin-dependent diabetes mellitus.

Patients with insulin-dependent diabetes mellitus (IDDM) have a high risk of developing diabetic nephropathy, retinopathy and cardiovascular diseases. The contribution of gene polymorphisms of the renin angiotensin system to these complications is controversial and may differ among populations. In 257 Dutch IDDM patients (188 with urinary albumin excretion (UAE) <30 mg/24 h), logistic regression analysis was used to study the relationships among, on the one hand, the insertion/deletion gene polymorphism of the angiotensin-converting enzyme gene (ACE-ID), the M235T gene polymorphism of the angiotensinogen gene (AGT-M235T), and the A1166C gene polymorphism of the angiotensin type 1 receptor gene (AT1-A1166C), and, on the other hand, UAE, retinopathy, hypertension, and coronary heart disease. The T-allele of the AGT-M235T polymorphism was associated with an increased risk of an elevated UAE (odds ratio (OR) 3.03; 95% confidence interval (CI) 1.06-8.61), but only when interaction with the D-allele of the ACE-ID polymorphism was considered. A previously described positive interaction between the T-allele of the AGT-M235T polymorphism and the D-allele of the ACE-ID polymorphism could not be confirmed. The T-allele was also associated with an increased risk of retinopathy (OR 3.89, 95% CI 1.79-8.47). The CC-genotype of the AT1-A1166C polymorphism was associated with hypertension (OR 3.58; 95% CI 1. 23-10.37). In a Dutch IDDM population, including 69 patients with (incipient) diabetic nephropathy, the T-allele of the AGT-M235T polymorphism is associated with an elevated UAE and diabetic retinopathy and the CC-genotype of the AT1-A1166C polymorphism is associated with hypertension. A previously described interaction between the AGT-M235T and the ACE-ID polymorphisms could not be confirmed. Since the number of nephropathic patients in this study is small, these conclusions must be interpreted with caution.

Insulin Dependent Diabetes Mellitus and Eating Disorders: A Literature Review

Ego development, independence, and self-concept are psychosocial issues which play an enormous role in the successful passage of youth through adolescence. This is a time of uncertainty and upheaval for the healthy teen. The onset of a chronic disease such as insulin dependent diabetes mellitus (IDDM) during this tumultuous period of development can disrupt the adolescent, and psychological problems and/or disorders such as depression, poor body image, and eating disorders can develop. A review of the literature tends to implicate stringent dietary restrictions and weight gain as predisposing factors in the incidence of eating disorders within this population. Also, low self-esteem, depression, and the struggle between autonomy and dependence are commonly associated with IDDM, as well as eating disorders. Although the association between diabetes mellitus and eating disorders is controversial, the magnitude of serious complications arising from the combination warrants further research. Eating disorders within the IDDM population interfere with glycemic control, in a population already hormonally tenuous in achieving this control, and predisposes the young individual to the many serious complications which arise from poor metabolic functioning. In order to adequately care for adolescents with IDDM, caregivers must look at the disease in a multidisciplined approach and consider the possibility of low self-esteem, depression, and/or an eating disorder.

IA-2, a transmembrane protein of the protein tyrosine phosphatase family, is a major autoantigen in insulin-dependent diabetes mellitus.

IA-2 is a 105,847 Da transmembrane protein that belongs to the protein tyrosine phosphatase family. Immunoperoxidase staining with antibody raised against IA-2 showed that this protein is expressed in human pancreatic islet cells. In this study, we expressed the full-length cDNA clone of IA-2 in a rabbit reticulocyte transcription/translation system and used the recombinant radiolabeled IA-2 protein to detect autoantibodies by immunoprecipitation. Coded sera (100) were tested: 50 from patients with newly diagnosed insulin-dependent diabetes mellitus (IDDM) and 50 from age-matched normal controls. Sixty-six percent of the sera from patients, but none of the sera from controls, reacted with IA-2. The same diabetic sera tested for autoantibodies to islet cells (ICA) by indirect immunofluorescence and glutamic acid decarboxylase (GAD65Ab) by depletion ELISA showed 68% and 52% positivity, respectively. Up to 86% of the IDDM patients had autoantibodies to IA-2 and/or GAD65. Moreover, greater than 90% (14 of 15) of the ICA-positive but GAD65Ab-negative sera had autoantibodies to IA-2. Absorption experiments showed that the immunofluorescence reactivity of ICA-positive sera was greatly reduced by prior incubation with recombinant IA-2 or GAD65 when the respective antibody was present. A little over one-half (9 of 16) of the IDDM sera that were negative for ICA were found to be positive for autoantibodies to IA-2 and/or GAD65, arguing that the immunofluorescence test for ICA is less sensitive than the recombinant tests for autoantibodies to IA-2 and GAD65. It is concluded that IA-2 is a major islet cell autoantigen in IDDM, and, together with GAD65, is responsible for much of the reactivity of ICA with pancreatic islets. Tests for the detection of autoantibodies to recombinant IA-2 and GAD65 may eventually replace ICA immunofluorescence for IDDM population screening.

Method-dependent increase in lipoprotein(a) in insulin-dependent diabetes mellitus during pregnancy

The current prevalent view is that plasma lipoprotein(a) [Lp(a)] concentrations are under strong genetic control. Most dietary and drug interventions seem to have little or no effect on plasma Lp(a) levels. However, evidence for a possible regulatory role of hormones is accumulating, for instance, fluctuations of Lp(a) levels during pregnancy have been reported. Also, in insulin-dependent diabetes mellitus (IDDM) patients, elevated Lp(a) levels have been reported. In the present longitudinal study, plasma lipid concentrations, including Lp(a), were determined in IDDM women before pregnancy, during pregnancy, and 3 months postpartum. In our study population, Lp(a) concentration was not significantly correlated with either hemoglobin A 1c (HbA 1c) levels or apolipoprotein(a) [apo(a)] phenotype. Changes in other lipid parameters observed during pregnancy in our IDDM population were similar to those reported during normal pregnancy. Lp(a) concentrations were quantified using two different immunochemical methods that possess different sensitivities and specificities: an immunoradiometric assay (IRMA) using two different anti-apo(a) antibodies, and an enzyme-linked immunosorbent assay (ELISA) using an anti-apo(a) and an anti-apo B antibody. Median prepregnancy Lp(a) concentrations were 118 mg/L (range, 15 to 672) as determined with the IRMA and 107 mg/L (range, 21 to 451) as determined with the ELISA. Women with IDDM showed, in general, no significant change in Lp(a) concentration during pregnancy when it was assayed with the IRMA, although a tendency to increased values was observed. When Lp(a) concentrations were determined with the ELISA, a strong and significant increase in Lp(a) from weeks 17 to 24 of pregnancy onward was found. The latter results confirm the prevalent view that during pregnancy Lp(a) levels are increased. However, the present results and those of others on Lp(a) in normal pregnancy strongly emphasize the importance of method selection when determining Lp(a) concentrations.

Insulin-dependent diabetes mellitus and the major histocompatibility complex peptide transporters TAP1 and TAP2: no association in a population with a high disease incidence.

Although many studies have established an association between insulin-dependent diabetes mellitus (IDDM) and the class II region of the human major histocompatibility complex (MHC), it has been difficult to assign susceptibility to a single locus. Recently, two antigen-processing genes, TAP1 and TAP2, have been identified within the region. Previous studies have reached conflicting conclusions as to the role of these genes in IDDM; it is uncertain whether an increased frequency of the allele TAP2A and a concomitant decrease in TAP2B are independent disease associations or secondary to linkage disequilibrium (LD) between TAP2A and HLA-DR3. To further investigate this question, we have characterized TAP1 and TAP2 alleles in 129 IDDM patients from Sardinia, a population with limited genetic heterogeneity and a high disease incidence. When compared to 90 random controls, the only significant difference was a decrease in the minor allele TAP2C in patients. However, when HLA-DR and -DQ matched controls were compared, this difference disappeared. Further analysis suggested that TAP2C was in LD with HLA-DRB1*1401 and subtypes of HLA-DRB1*11, alleles which were not observed in the IDDM population. LD was also observed between other TAP and HLA-DR alleles, in particular between TAP2A and HLA-DR3 in both patients and controls. Our data supports the conclusion that there is no primary association between TAP2 alleles and IDDM, and that previously reported associations may be due to LD with other class II loci.

Serum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus

The activity of serum paraoxonase, an enzyme located on high-density lipoprotein, has been investigated in familial hypercholesterolaemia (FH) and insulin dependent diabetes mellitus (IDDM). Increases in total serum cholesterol and apolipoprotein B were present in both FH and IDDM compared to healthy controls and in the patients with IDDM, serum triglycerides were also raised. The serum HDL-cholesterol concentrations in controls and patients with FH and IDDM did not differ significantly. Serum paraoxonase activity was significantly lower in both the FH and IDDM populations than in controls ( P < 0.001 and P < 0.01, respectively). 72% of the FH population and 67% of the IDDM population were in the lower half of the frequency distribution for serum paraoxonase (activity of < 112 U/l). It is likely that the common factor related to low paraoxonase activity is hyperlipidaemia. It is possible that paraoxonase has a physiological role in lipid metabolism and that decreases in its activity may accelerate atherogenesis.

Employment Spectrum of IDDM

Occupational issues in 158 insulin-dependent diabetes mellitus (IDDM) individuals and 158 matched nondiabetic siblings were examined in a case-control design to evaluate the role of diabetes in the employability of people with IDDM. Overall, the IDDM cases were more likely to report refusal for a job at some point in their lives (56 vs. 42%, P = .02) than were the nondiabetic control siblings. Surprisingly, individuals who told job interviewers about their diabetes were more likely to report job refusal than their siblings (64 vs. 42%, P = .005), whereas individuals who did not mention their diabetes reported rates of refusal similar to their siblings (44 vs. 41%). IDDM cases were also less likely to be employed full time compared with siblings (55 vs. 73%, P = .001). Reduced employment in IDDM respondents was related to work disability. Reported work disability was more than seven times greater in the IDDM than the sibling group. The presence of diabetic complications was the primary factor related to work disability. Although 13% of IDDM respondents were unable to work because of disability, absenteeism among IDDM cases currently working did not differ from that of the nondiabetic siblings. Diabetes was not significantly associated with career levels or household income levels reported by the IDDM group. Disability, however, had a strong detrimental influence on these variables. The results suggest that hiring practices by employers may still be discriminatory toward individuals with IDDM. Once hired, the employment experiences of the IDDM population appear to be similar to the experiences of the nondiabetic population, provided the development of disabling diabetic complications has not taken place.

Association of HLA-DR phenotypes and T-lymphocyte-receptor beta-chain-region RFLP with IDDM in Japanese.

Fifty Japanese patients with insulin-dependent diabetes mellitus (IDDM) and 94 normal subjects were genotyped for BglII restriction-fragment-length polymorphism (RFLP) of the T-lymphocyte-receptor beta-chain (TLR beta)-region gene and analyzed in relation to HLA-DR phenotypes. The antigen frequencies of DR4 and DR9 in the IDDM population were significantly higher than those in the normal population, with relative risks of 1.87 (P less than .02) and 2.42 (P less than .01), respectively. Hybridization of digested DNA with the TLR beta probe revealed two alleles of 9.3 and 8.6 kilobases (kb). The allele frequency of 8.6 kb in patients with IDDM (79%) was significantly (P less than .05) higher than that in normal subjects (64%). When TLR beta-region RFLP in IDDM was further analyzed with respect to the HLA-DR phenotypes, the frequency of 8.6 kb was significantly increased in patients with DR4 but not DR9 (DR4/X) and those with DR9 but not DR4 (DR9/X) compared with the frequency found in normal subjects (P less than .05); the relative risks of 8.6 kb in DR4/X and DR9/X were 2.77 and 4.98, respectively. Although the frequencies of HLA-DR phenotypes and of TLR beta-region RFLP in IDDM and normal subjects were apparently different from those reported for Caucasians, this population-association study indicates that in the Japanese, genes conferring susceptibility to IDDM exist near or at the HLA-DR and the TLR beta loci, as has been demonstrated in Caucasians.

Sequence analysis of HLA class II genes from insulin-dependent diabetic individuals

To examine the nature of HLA-linked genetic susceptibility to insulin-dependent diabetes mellitus (IDDM), we compared HLA class II gene sequences from IDDM patients and control individuals. Genomic libraries were constructed from two siblings with IDDM, typed serologically as DR3,w6 and DR3,4. These libraries represent the HLA haplotypes (DR3, DR4) most frequently associated with IDDM, as well as one haplotype found less often. Individual genomic clones were identified and assigned to specific loci and haplotypes. The nucleotide sequence was then determined from the variable second exon from the HLA-DQα, DQß, and DRß genes from all three haplotypes. Sequence variation within the DQα genes could not be correlated with the disease. For all three haplotypes, the DQα sequence from the IDDM patient was identical to the DR-matched control sequence. Similarly, for the DR3 haplotype, the DQß sequences matched all control DR3 alleles. The DQß sequence from the DR4 haplotype was identical to the predominant DR4 allele (DQß 3.2) but differed at four amino acid residues from the other major DR4 DQß sequence (DQß3.1) found rarely among IDDM patients. Sequence analysis of the DQß gene from the DRw6 haplotype revealed a new allele that differed from the DQß allele from a control DR6 allele at two residues. The DRß genes from these three haplotypes also did not show any sequence features uniquely associated with IDDM, although the frequency of certain allelic variants in all three of these haplotypes may be altered in the IDDM population. A particular group of amino acids was found to be shared between the DRß-1 alleles from the DR4 and DRw6 haplotypes and may be involved in genetic susceptibility to IDDM.

Genetic, immunologic, and environmental heterogeneity of IDDM. Incidence and 12-mo follow-up of an Italian population.

The 1-yr incidence of insulin-dependent diabetes mellitus (IDDM) in a population of the Piedmont and Aosta Valley area of Italy was recorded. Anti-virus antibodies (e.g., Coxsackie B1-6, mumps, cytomegalovirus), islet cell antibodies (ICAs), and HLA-A, -B, -C, and -DR were determined in 74 IDDM patients (38 males, 36 females) and in controls. Total IDDM incidence was 5.0/100,000, and the incidence for those less than 20 yr of age was 11.6/100,000. Anti-virus antibody frequency was not different in IDDM patients and controls. ICAs were present in 58% of IDDM patients at onset and in 30% after 12 mo, and complement-fixing ICAs were found in 39 and 17%, respectively. IDDM was significantly and positively associated with DR3/DR4 and negatively associated with DR2 and DR5. ICA frequency was significantly higher in DR3/DR4 heterozygote patients than in patients without DR3 and DR4. These results suggest that in this IDDM population viral etiology is not evident, ICAs offer only a partial pathogenetic explanation, and genetic and immunologic heterogeneity is evident.

HLA-DR4 in insulin-dependent diabetic parents and their diabetic offspring: a clue to dominant inheritance.

Insulin-dependent diabetes mellitus (IDDM) susceptibility determinants are known to be associated with both HLA-DR3 and -DR4. We monitored the inheritance of HLA-DR alleles in 37 families in which IDDM affected one parent and at least one offspring in order to try to learn more about the modes of inheritance of IDDM determinants. Ninety-seven insulin-dependent diabetics whose parents did not have diabetes and 158 nondiabetics were used as control groups for estimates of DR allele frequencies in the overall diabetic and general populations. The proportion of diabetic parents who transmitted DR4 to diabetic offspring (78%) was significantly higher (P less than 0.001) than the gene frequency of DR4 in the overall diabetic population (43%). The proportion of nondiabetic parents who transmitted DR4 to diabetic offspring (22%) was not significantly different from the gene frequency of DR4 in the nondiabetic population (16%), but it was significantly lower (P less than 0.05) than the gene frequency in the overall IDDM population. These proportions suggest that inheritance of the DR4-associated IDDM susceptibility determinant is not recessive, because in recessive inheritance expression of a trait depends on each parent contributing a susceptibility determinant. The proportions of diabetic and nondiabetic parents who transmitted the DR allele associated with the susceptibility determinant would then equal one another. The transmission of predominantly DR4 from affected parents to affected offspring suggests that susceptibility to IDDM is inherited primarily via a single dose of a potent determinant associated with DR4, as in dominant inheritance. When DR3 was transmitted at all it was usually by the nondiabetic parent. Only 8% of diabetic parents transmitted DR3 but 35% of nondiabetic parents transmitted DR3. The proportion of nondiabetic parents who transmitted DR3 was similar to the gene frequency of DR3 in the overall diabetic population (29%), but it was significantly higher than the gene frequency of DR3 in the nondiabetic population (15%; P less than 0.005). The percentage of diabetic offspring with the genotype DR3DR4 (35%) was identical to the percentage of individuals in the overall IDDM population with this genotype (35%). Numerous population data indicate that the DR3DR4 genotype carries a higher relative risk for IDDM than any other genotype, which suggests synergism between the DR3- and DR4-associated determinants. The family data reported here support this synergism but suggest that the DR4-associated determinant can give substantial susceptibility independent of the DR3-associated determinant and that the DR3-associated determinant is often expressed as enhancing susceptibility in the presence of the dominant DR4- associated determinant.

HLA-DR antigen frequencies in a North Indian type I diabetic population.

Eighty-eight North Indian patients with type I, insulin-dependent diabetes mellitus (IDDM) and 113 unaffected individuals were typed for HLA-DR antigens from DR1 to DR7. The frequency of HLA-DR3 was significantly increased in the patients as compared with the controls (78.4% versus 25.7%, corrected P = 1.68 X 10(-12], the relative risk (RR) of 10.52 being much higher than that reported in the Western IDDM population. HLA-DR2 showed a significant negative association (RR = 0.18, corrected P = 1.03 X 10(-5], but DR4 had no relationship with IDDM in the present study (RR = 1.12, P = 0.12). These results emphasize the differences in HLA-IDDM associations among different ethnic groups.