PreDiabetes: Treatment Options
Future therapeutic Options:
ACE inhibitors following the HOPE study have gained importance in this area. Data with regard to diabetes prevention in the5700 patients in the HOPE study is based on SELF REPORTING! No formal GTT testing results were available pre or post and hence IGT status was not known in these patients. The self reporting revealed incidence of T2DM in the Ramipril and Placebo groups of 3.5% and 5.4% respectively ( a 33% risk reduction).
Mechanisms of ACE inhibitor efficacy in improving glucose tolerance:
ACE Inhibitors improve muscle blood flow and increase muscle glucose uptake (increase GLUT4 activity). They suppress brain sympathetic activity thus improving insulin sensitivity. They may have an effect on the tissue ACE demonstrated in pancreatic beta cells. Increasing the bradykinin and prostaglandins in the muscle has been shown to improve insulin sensitivity of muscle and this could be a possible mechanism.
Angiotensin Receptor blockers:
Losartan in LIFE study produced a 25% risk reduction in diabetes incidence, probably in normoglycaemic individuals. But this trial was against atenolol. Did atenolol increase diabetes incidence?
Candesartan in the CHARM trial also showed a 20% risk reduction in diabetes.
Statins:
(Pravastatin) though shown to possibly decrease the incidence of diabetes compared to placebo, has never been demonstrated to delay progression of glucose intolerance in high risk individuals as those with established IGT. 139 men developed diabetes over a 5 year period out of 5900 euglycemic men in the WOSCOPS study. This was a 30% risk reduction in the Pravastatin group. Similar findings were not noted in the HPS.
GLP-1
Known as an incretin, GLP-1 decreases the islet threshold for insulin secretion for a given glucose level. Obese patients have a lower level of GLP-1 with a degree of resistance to this gut derived hormone. This could contribute to the decreased insulin response which characterizes the failing pancreas in the IGT patient. Replacing with the effective pharmacological rather than physiological doses of this hormone is limited by its short half life and problems with feasible routes of administration. Exendin9-39, a GLP-1 agonist, is a budding oral therapeutic option which could delay or prevent progression of mild degrees of dysglycaemia by "resting" the pancreas. Read further.....
Avoiding diuretics to prevent worsening of glucose intolerance??
An additional 7 cases of new biochemical diabetes were observed over 4 years in every 1000 patients randomized to chlorthalidone. While diuretics are favoured as initial therapy in most hypertension guidelines, special circumstances (obesity/glucose intolerance/diabetes) should evoke a physician preference for other modalities of therapy (ACEI/ ARBs)
Avoiding Beta blockers to prevent worsening of glucose intolerance?
Special circumstances need to be considered when initiating antihypertensive therapy as is currently recommended in the BHS guidelines. While patients with angina or IHD need to be strongly considered for a beta blocker as initial or early therapy, an obese subject or a patient with IGT should be considered for an alternative modality of anti-hypertensive therapy. Blood pressure reduction, achieved by any means, probably is equally effective irrespective of the modality used. This has been fairly consistently borne out in most hypertension studies. While blockade of catecholamines in the periphery might have beneficial effects on glucose intolerance, this is probably offset by the effect of beta blockade at the pancreatic beta cellular level.
ACE inhibitors following the HOPE study have gained importance in this area. Data with regard to diabetes prevention in the5700 patients in the HOPE study is based on SELF REPORTING! No formal GTT testing results were available pre or post and hence IGT status was not known in these patients. The self reporting revealed incidence of T2DM in the Ramipril and Placebo groups of 3.5% and 5.4% respectively ( a 33% risk reduction).
Mechanisms of ACE inhibitor efficacy in improving glucose tolerance:
ACE Inhibitors improve muscle blood flow and increase muscle glucose uptake (increase GLUT4 activity). They suppress brain sympathetic activity thus improving insulin sensitivity. They may have an effect on the tissue ACE demonstrated in pancreatic beta cells. Increasing the bradykinin and prostaglandins in the muscle has been shown to improve insulin sensitivity of muscle and this could be a possible mechanism.
Angiotensin Receptor blockers:
Losartan in LIFE study produced a 25% risk reduction in diabetes incidence, probably in normoglycaemic individuals. But this trial was against atenolol. Did atenolol increase diabetes incidence?
Candesartan in the CHARM trial also showed a 20% risk reduction in diabetes.
Statins:
(Pravastatin) though shown to possibly decrease the incidence of diabetes compared to placebo, has never been demonstrated to delay progression of glucose intolerance in high risk individuals as those with established IGT. 139 men developed diabetes over a 5 year period out of 5900 euglycemic men in the WOSCOPS study. This was a 30% risk reduction in the Pravastatin group. Similar findings were not noted in the HPS.
GLP-1
Known as an incretin, GLP-1 decreases the islet threshold for insulin secretion for a given glucose level. Obese patients have a lower level of GLP-1 with a degree of resistance to this gut derived hormone. This could contribute to the decreased insulin response which characterizes the failing pancreas in the IGT patient. Replacing with the effective pharmacological rather than physiological doses of this hormone is limited by its short half life and problems with feasible routes of administration. Exendin9-39, a GLP-1 agonist, is a budding oral therapeutic option which could delay or prevent progression of mild degrees of dysglycaemia by "resting" the pancreas. Read further.....
Avoiding diuretics to prevent worsening of glucose intolerance??
An additional 7 cases of new biochemical diabetes were observed over 4 years in every 1000 patients randomized to chlorthalidone. While diuretics are favoured as initial therapy in most hypertension guidelines, special circumstances (obesity/glucose intolerance/diabetes) should evoke a physician preference for other modalities of therapy (ACEI/ ARBs)
Avoiding Beta blockers to prevent worsening of glucose intolerance?
Special circumstances need to be considered when initiating antihypertensive therapy as is currently recommended in the BHS guidelines. While patients with angina or IHD need to be strongly considered for a beta blocker as initial or early therapy, an obese subject or a patient with IGT should be considered for an alternative modality of anti-hypertensive therapy. Blood pressure reduction, achieved by any means, probably is equally effective irrespective of the modality used. This has been fairly consistently borne out in most hypertension studies. While blockade of catecholamines in the periphery might have beneficial effects on glucose intolerance, this is probably offset by the effect of beta blockade at the pancreatic beta cellular level.