This study demonstrates that DM is highly frequent among admitted TB patients in Mulago hospital, Uganda. To our knowledge, this is the first study to examine this association in Uganda, one of the high burden TB countries in SSA. The reported prevalence of DM among the TB patients of 8.5% is significantly higher than the estimated prevalence of DM among the general population in Uganda (2.2%) [4
] and the back ground prevalence of DM on the medical units in the hospital during the study period (6.4%).
The documented prevalence of DM among TB patients in the African studies published between 1980 and 2006 varies between 2.1%-6.7% [14
]. The observed prevalence of DM among TB patients in our study is comparable to that reported from Nigeria [16
] and Tanzania [17
] but higher than what was noted in South Africa [14
] and Guinea Conakry [15
This heterogeneity in the above results could probably be explained by the varied techniques used to diagnose DM among the TB patients and the probable effects of co morbidities like HIV. Largely, an oral glucose tolerance test (OGTT) was used in diagnosing DM in most African studies [14
]. Balde et al. used a fasting capillary blood test to diagnose DM among TB patients in Guinea Conakry [15
]. In our study, the diagnosis of DM was made basing on a random or casual capillary blood test. No particular method of diagnosing DM among TB patients has been advocated for. Either a random blood sugar (RBS), fasting blood sugar (FBS), OGTT or glycated haemoglobin (HbA1c) test can be used alone or in combination [5
Similar studies from other parts of the world have reported remarkably higher prevalence of DM among TB patients. In Asia and the Middle East, the documented prevalence varies from 9.5%-44% [13
] and 11.9%-27% [24
] respectively. A multi centre study done in Texas, USA and Mexico reported prevalence of 39% and 36% respectively [27
]. This higher prevalence could probably be due to the higher background prevalence of DM in the general population in those respective countries.
Type 2 DM was the most frequent type of DM encountered among the study participants with DM-TB co-infection (90.9%). A similar observation has been documented in most similar studies [13
]. This could probably be due to the higher proportions of people with type 2 DM compared to type 1 DM in most general populations.
Five (1.9%) of the study participants at enrolment had a prior diagnosis of DM and on assessment to determine the extent of glycemic control, they all had poor glycemic control which we defined as a RBS level ≥ 180 mg/dl. TB infection is often associated with a transient stress induced hyperglycemia which results into suboptimal glycemic control among diabetic patients. It usually resolves following TB therapy [28
This form of reactionary hyperglycemia can also lead to over diagnosis of DM among TB patients. Studies by Alisjahbana et al. [13
], Oluboyo et al. [16
] and Mugusi et al. [17
] demonstrated improvement in the glycemic status of some patients following TB treatment. However in our study, we did not perform a repeat assessment of the glycemic status among the newly diagnosed DM patients during the course of TB therapy.
HIV co-infection and raised mean serum ALT concentrations were noted to be independently associated with DM among TB patients in our study. In contrast to available literature and findings from other studies [29
], HIV infection appeared protective in our study. A probable explanation for this is that most of our HIV positive patients were taking cotrimoxazole prophylaxis, a drug which has been found to cause hypoglycaemic effects in some patients [34
]. However, this relationship between HIV and DM in our study needs to be interpreted with caution. This is because a study done in this similar setting to determine glycemic levels in patients with severe sepsis (80% of whom also had HIV infection and were on cotrimoxazole prophylaxis) revealed no statistically significant association between HIV infection and hyperglycemia (OR-0.97, 95%CI 0.57-1.62) [35
Raised mean serum ALT concentrations in TB/DM patients have not been described in any similar studies. However, since majority of the study participants had HIV co-infection, an elevated mean ALT concentration of >66 U/L prior to diagnosis of DM was noted to be significantly associated with DM among HIV infected patients in one case control study performed in an urban HIV clinic in the USA [33
A raised mean serum ALT concentration is a strong predictor of insulin resistance [36
]. It also principally reflects direct hepatocellular damage or liver dysfunction. Liver dysfunction secondary to underlying hepatitis C and hepatosteatosis have been demonstrated to be associated with DM [37
Hepatitis C infection is associated with insulin resistance owing to an increased pro-inflammatory state and production of cytokines especially tumour necrosis factor α and interleukin 6. These inhibit transcription of the glucose transporter-4 and peroxisome proliferator –activated receptor γ. Insulin resistance results into alteration in lipid metabolism and deposition in the hepatocytes. Hepatosteatosis often develops later. Hepatitis C co-infection is also associated with autoimmune pancreatic beta cell damage leading to DM [37
]. In addition to hepatitis C infection, human herpes virus type 8 (HHV-8), a highly prevalent virus among HIV infected patients that causes with kaposi sarcoma has also been demonstrated to be linked to ketosis prone type 2 DM, an atypical form of DM commonest among black Africans [41
]. In our study however, we did not assess for presence of hepatosteatosis, hepatitis C or HHV-8 co-infection among the study participants.
Majority of the similar studies have reported increasing age, overweight or obesity [15
] and male gender [20
] as the clinical factors associated with DM among TB patients. Sedentary lifestyle and family history of DM and obesity were also noted to be independently associated with DM in the study done in Guinea Conakry [15
]. These clinical factors were not significantly associated with DM among our study participants.
We acknowledge important limitations in our study. Only one RBS estimation was used to diagnose DM hence leading to a possibility of overestimating of the prevalence of DM among our study participants since patients with reactive hyperglycemia could have been included. Use of an OGTT could have diagnosed more patients with borderline DM.
Although the study adjusted for some of the confounding factors, the role of residual confounding factors for the association between DM and TB cannot be ruled out. In addition, due to the cross sectional nature of the study, the temporality between the TB and DM could not be ascertained.
As similar findings have been documented among TB patients in other parts of the world, we believe that our findings are generalisable and hence we recommend that patients diagnosed with TB should routinely have their blood sugar levels assessed in order to enable timely diagnosis and optimal management of DM.