8.1 Diabetes

Diabetes is a common condition, particularly in some countries, where up to 30–40% of TB patients are affected. The population attributable fraction of diabetes as a risk factor for TB is more than 10% in all WHO regions, except for Africa and the Western Pacific (5). Diabetes was estimated to account for more than 10% of global TB deaths among HIV-negative individuals (60).

Hyperglycaemia induces abnormalities in both the innate and adaptive immune response to M. tuberculosis, and diabetes increases the risk (twofold to fourfold) that TB infection will progress to disease; also, the response to treatment is often worse in those with diabetes. Among the mechanisms involved, bacterial recognition and phagocytosis are less effective in diabetes, with impairment of antigen-presenting cell recruitment and delay in activating the cellular immune response (61). Clinically, this translates into an increased proportion of sputum smear positive patients, with more extensive pulmonary disease bilaterally, larger number of cavities and lymph node enlargement, and “atypical” findings of lower lobe lesions (especially in patients with poor glycaemic control). People with diabetes also suffer an increased rate of failure and death, and a higher risk of relapse (61).

Diabetes has a negative effect on the pharmacology of some anti-TB drugs (e.g. rifampicin), with higher risk of development of drug-resistance (61). Rifampicin is a potent hepatic enzyme inducer, increasing the hepatic metabolism of sulphonyl urea derivatives and therefore lowering their plasma levels. No effect of rifampicin is known on the exposure of glucagon-like peptide-1 receptor agonists and only a slight effect on dipeptidyl peptidase-4 inhibitors. Although metformin is not metabolized by the P450 enzymes system, its hypoglycaemic effect may be increased by rifampicin, enhancing the expression of organic cation transporter and the hepatic uptake of metformin. Because insulin is not metabolized, no pharmacokinetic interactions with anti-TB drugs occur; therefore, some authors have recommended that it be used at the beginning of TB treatment, to achieve faster bacteriological sputum conversion and prevent drug–drug interactions (61).

A higher proportion and sometimes a greater severity of adverse events has been described in TB patients with diabetes (e.g. peripheral neuropathy due to isoniazid and ocular neuropathy due to ethambutol) (61).

There is evidence that the problems described above reduce when diabetes is well controlled. Therefore, adequate control of diabetes, and collaboration between TB and diabetes services, are important, particularly in countries with a high prevalence of diabetes.

Implementation considerations

  • Although the drugs used to treat DS-TB are generally well tolerated and are unlikely to cause serious adverse events among people with diabetes, treatment monitoring is important to ensure rapid notification and prompt management of any side-effects that eventually appear.
  • Management of these patients involves a multidisciplinary approach, in view of the additional need to control diabetes and the potential need to adjust drug dosing. A national or subnational body supporting the management of people with difficult-to-treat TB (i.e. a consilium) may be of help in specific cases
  • Supporting adherence is an important management component when treating people with DS-TB and diabetes. Therefore, collaboration with partners in the community, including family members, carers, health care workers and welfare workers, is essential.
  • Coordination of NTPs with diabetes services may be relevant in countries where TB is highly prevalent.

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