The prevalence of LADA in this report was found to be 14%. This finding is comparable to previous reports from Ghana where documented prevalence rates for LADA amongst people being managed for type 2 DM was 13.5% [10
]. [Lutale et al 28
] found low prevalence of antiGAD and ICA islet antibodies (7.3%) amongst Type 2 DM patients in Tanzania.
Majority of the subjects with LADA in this study were in 50–59 age category and less than 5% were in the 30–39 age category. This observation suggests that LADA increases with increasing age decade, confirming reports by [Carlson et al 29
] that older age was an important risk factor for LADA as for Type 2 DM and this may suggest a potential role for insulin resistance in the pathogenesis of LADA. A Chinese report also noted that the prevalence of LADA slowly increased with age up to 60
years and was high in individuals aged 50–59
]. [Horton et al 30
] reported that genetic influences were determinants of age at presentation in LADA specifically the DRB1/DQB1 genotype with younger LADA subjects demonstrating this genotype while little relation to a specific genotype occurred after the age of 55
Our findings lend credence to previous reports which suggest that the presence of LADA is non sex specific [9
]. We have documented in this report that although a higher percentage (64%) of subjects positive for antiGAD autoantibodies in this study were females, the prevalence rates were however comparable in both sexes.
Thirty-seven percent of LADA were already on insulin as at the time of the Study for glycaemic control and this may be a reflection of autoimmune destruction of the β cells which has been reported to be present at diagnosis of DM in LADA patients [31
]. This documented observation is not surprising given the fact that we uncovered insulinopaenia in 60% of our Study subjects (that were antiGAD autoantibody positive) who were on insulin. The Hoorn study involving 50–74
year old population reported an association between GAD positivity and insulin use in diabetic subjects [32
]. In comparison, 19% of GADA negative individuals were on insulin for glycaemic control in this study, the proportion of LADA subjects on insulin was markedly higher.
The occurrence of other autoimmune antibodies with increased frequency of serologic markers of thyroid and adrenal disease in LADA has been well documented in various studies [33
]. Eleven percent of LADA patients in this study were found to have history of autoimmune thyroid disease, also confirming earlier reports of increased incidence of humoral immunity to other organ specific autoantibodies especially the thyroid gland [36
]. The Ehime study in Japan which followed up a cohort of LADA subjects noted, that positive thyroid peroxidase antibodies(Abs) and antithyroglobulin Abs contribute to the progression to B-cell failure in LADA [38
Less than 50% of subjects with LADA had a history of hypertension and about 30% had history of dyslipidemia. The proportion of LADA subjects with metabolic risk factors of overweight/obesity, hypertension, dyslipidaemia, smoking and alcohol ingestion was lower than GADA –ve subjects with these metabolic risk factors. Similar findings have been reported from Ghana, China, Sweden and Australia [10
]. The aforementioned Ghanaian study (10) found that LADA differed from autoantibody negative type 2 DM in hypertension and central obesity which occurred more frequently in the latter, concluding that generally, clinical and metabolic markers could not be used to differentiate Ghanaian latent autoimmune diabetes from type 2 DM. The proportion of obese/overweight among subjects with LADA in this study was higher than those in normal/underweight category and this suggests insulin resistance as possible contributory factor in the pathogenesis of LADA amongst our patients.
About half of LADA subjects in this study were insulinopenic. Although patients with LADA share insulin resistance with type 2 diabetes patients, they however display a more severe defect in stimulated beta-cell capacity than patients with classical type 2 diabetes. This observation suggests that C-peptide levels could be used as a clinical screening tool in identifying LADA. [Bell and Ovale 41
] in a study to assess the effectiveness of random C-peptide levels as screening test for LADA noted that LADA can be ruled out in adult-onset diabetes by the presence of elevated C-peptide.
A higher proportion of subjects with LADA had evidence of microvascular complications of DM namely retinopathy and neuropathy and a higher proportion of GADA –ve individuals manifested nephropathy. The prevalence of dyslipidemia and the metabolic syndrome was also higher in the GADA-ve group. The foregoing would suggest that macrovascular complications of DM were more frequent in GADA-ve patients, while LADA subjects manifest predominantly microvascular complications especially retinopathy. The poor indices of long term glycemic control in LADA may account for the observed higher percentage of LADA subjects with evidence of microvascular DM complications. [Myhill et al 42
] noted that subjects with LADA compared with the GAD antibody-negative patients, had a similar prevalence and incidence of coronary heart, cerebrovascular disease, cardiac disease and all-cause mortality. The significant proportion of LADA with retinopathy observed in this study is similar to reports from Turkey [43
]. Reports from Western Finland [9
] however noted similar prevalence of retinopathy, cardiovascular morbidity and mortality between LADA and GADA-ve subjects and glycaemic control was noted to be a stronger risk factor for cardiovascular disease in LADA subjects.