From this study, we can only learn that atenolol is less effective than amlodipine, but we cannot blame the diuretic in the worse outcome. The amlodipine and hydrochlorothiazide components of the single pill combination could be titrated to 25 and 10 mg, respectively.

Although the dose of amlodipine in the trial was similar to that demonstrating favorable outcomes in other outcome trials, the dose range for hydrochlorothiazide Information on supplemented antihypertensive agents was not reported, but the recommended supplementary drugs were α- and β-blockers, for which effects on CV outcomes are inferior.

Of note, a small but significant BP difference 0. The results of this study raised the question whether all thiazide-type diuretics are equal. A meta-analysis of trials done until reported similar clinical CV outcomes across the class However, these studies used doses of these agents that were higher than the Recent data suggest that chlorthalidone is 1.

Thus, to achieve the beneficial effect with diuretics, one should use hydrochlorothiazide in a dose of up to at least Another thiazide-like diuretic that is less discussed is indapamide.

This agent has less adverse effect on metabolic parameters than other diuretics 45 , 46 , is more effective than enalapril in reducing left ventricular mass 47 , is equivalent to enalapril in reducing microalbuminuria 48 , and is effective in reducing CV morbidity and mortality in clinical trials 3 , 9 , 16 , Thus, the use of indapamide as a leading diuretic agent may be worthwhile.

There is no evidence from systematic overviews and meta-analyses that thiazide diuretics are superior to other classes of antihypertensive drugs in reducing CV risk These results endorse the position of the European guidelines, which leave to the doctor the choice and flexibility of choosing among available antihypertensive drugs on the basis of several considerations, including efficacy, tolerability, compelling indications, contraindications, race, and cost.

ALLHAT was perceived as the trial that conclusively demonstrated the superiority of diuretics over other classes of antihypertensive drugs.

The doxazosin arm was prematurely stopped because of a significantly higher incidence of HF. It is frequently forgotten that the ALLHAT study failed to demonstrate its primary goal because the incidence of the primary end point did not show any statistical differences between the chlorthalidone group and any other treatment group 6-year event rate: chlortalidone Compared with chlorthalidone, the relative risks were 0.

Furthermore, all-cause mortality did not differ between the groups 4. The only significant differences in ALLHAT emerged in the analysis of some secondary end points. Thus, patients allocated to drugs different from chlorthalidone were more likely to regain fluids, with potential rapid disclosure of signs and symptoms of heart failure.

Consistent with this view is the early divergence of the Kaplan-Meier curved after randomization. However, subsequent post hoc analyses with validation of HF events and adjustment for pre-entry diuretic use seemed to confirm the original results Thus, ALLHAT did not meet its primary goal, and the evidence of superiority of chlortalidone over comparators was based on the analysis of secondary end points.

Furthermore, results obtained with chlorthalidone cannot be extrapolated to hydrochlorothiazide or other thiazide diuretics. The duration of the antihypertensive effect of chlorthalidone is significantly longer than that of hydrochlorothiazide, as evidenced by h ambulatory BP monitoring The results of ALLHAT are consistent with the INSIGHT study, which failed to detect outcome differences between a diuretic hydrochlorothiazide plus amiloride and a calcium antagonist nifedipine in a long-acting gastrointestinal transport system in 6, hypertensive patients aged 55—80 years.

Another major study that failed to demonstrate the superiority of diuretics over comparators was the ANBP2 trial. This was a randomized open-label study between diuretics and ACE inhibitors conducted in 6, elderly subjects with hypertension.

The ACE inhibitor enalapril and the diuretic hydrochlorothiazide were recommended as initial therapy, but the final choice of the specific agent was left to investigators, who were family practitioners. The primary end point of the study, a composite of CV morbidity and all-cause mortality, was marginally less frequent in the ACE inhibitor group than in the diuretic group hazard ratio [HR] 0.

ASCOT-BPLA Blood Pressure—Lowering Arm was a multicenter randomized controlled trial conducted in 19, hypertensive patients aged 40—79 years who had at least three other CV risk factors.

Patients were randomized to a first-line treatment with either atenolol or amlodipine. In the case of lack of BP control, bendroflumethiazide was added to atenolol and perindopril to amlodipine. The trial was stopped prematurely after 5. The primary end point, a composite of nonfatal myocardial infarction and fatal CHD, did not differ between the groups HR 0.

Although the benefits of amlodipine and perindopril over atenolol and bendroflumethiazide appeared to be largely driven by the 2.

The trial was prematurely stopped after a mean follow-up of 36 months because the boundary of the prespecified stopping rule was exceeded.

Also, the composite secondary end point death from CV causes, nonfatal myocardial infarction, and nonfatal stroke was less frequent in the benazepril-amlodipine group than in the benazepril-hydrochlorothiazide group HR 0. These data may relegate thiazide diuretics to third-line therapy.

However, since the study population was composed of complicated patients with hypertension and prior history of CHD, diabetes, or organ damage, it is unclear to what extent these findings can be extrapolated to less uncomplicated hypertensive subjects.

Diuretics increase the risk of NOD. In a network meta-analysis of 22 clinical trials, ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, and placebo were associated with a significantly lesser risk of NOD compared with diuretics The risk of NOD did not differ between diuretics and β-blockers Importantly, NOD was not a prespecified primary end point in any of these trials.

Diuretic-induced hypokalemia is believed to be one possible cause of the rise in glucose 52 , perhaps through an impaired insulin secretion by pancreatic β-cells. Also diuretic-induced hyperuricemia was associated with impaired glucose tolerance.

The controversy surrounding the issue of NOD in treated hypertensive subjects is not focused on the diabetogenic effect of diuretics and β-blockers, which is taken for granted 1 , but on the controversial interpretation of the few data on the prognostic impact of NOD induced by these drugs.

In a cohort study from our group, NOD portended a risk for subsequent CV disease that was not dissimilar from that of previously known diabetes.

Notably, plasma glucose at entry and diuretic treatment at the follow-up visit were independent predictors of NOD Individuals who are skeptical about the adverse prognostic value of NOD argue that NOD failed to translate into a prognostic disadvantage in most trials.

In the ALLHAT study, the higher incidence of NOD in the chlorthalidone group did not translate into a prognostic burden in this group, and a similar situation occurred in other studies However, a frequently forgotten consideration is that different risks of NOD are unlikely to translate into different risks of hard end points in the setting of available mega-trials.

Consequently, even large trials such as ALLHAT may be under-powered to detect the adverse prognostic impact of NOD However, when the chlorthalidone, amlodipine, and lisinopril groups were analyzed separately, the excess risk of coronary artery disease was significant only in the lisinopril group HR 2.

The power of the chlorthalidone and amlodipine groups might have been inadequate to detect the adverse impact of NOD on coronary artery disease demonstrated in the total ALLHAT cohort. We argued that the lesser BP reduction in the lisinopril group compared with the other groups might have allowed NOD to unveil its adverse prognostic impact In line with this interpretation, in a post hoc analysis of the SHEP study, NOD was associated with a higher risk of all-cause mortality HR 1.

Because the SHEP population was composed by elderly hypertensive patients at high risk of events in the short term, the favorable prognostic impact of BP reduction in the active treatment group may have outweighed the adverse prognostic impact of NOD. In conclusion, we should refrain from underestimating the adverse prognostic impact of NOD induced by diuretics and β-blockers, alone or combined, solely because of the failure by most randomized trials to disclose a significant association between NOD and outcome.

NOD, whether or not induced by drugs, remains an important adverse prognostic marker that should be prevented. We suggested that in subjects at increased risk of NOD impaired fasting glucose, obesity, metabolic syndrome , diuretics and β-blockers should 1 be used cautiously, with the lowest effective dose and plasma glucose periodically checked, and 2 be avoided in subjects with BP normalized by different classes of antihypertensive drugs.

In a meta-analysis of studies 57 , diuretics increased cholesterol and triglyceride levels, and the rise in total cholesterol was paralleled by a rise in LDL cholesterol. The rise in cholesterol was dose dependent and greater in blacks. A reduction in the HDL cholesterol levels was noted only in patients with diabetes.

The potentially adverse prognostic impact of increased total and LDL cholesterol in the very long term may be underestimated by the relatively short duration generally 3—5 years of available intervention trials.

When dealing with a young hypertensive patient, it is unlikely that an expected persistent elevation of total and LDL cholesterol over decades may be beneficial. The long-term use of diuretics was associated with an increased risk of renal cell carcinoma. In a meta-analysis, Grossman et al.

The renal tubular cells, which are the main target of diuretics, are also the site of origin of malignancy.

The association between diuretic treatment and renal cell carcinoma is a potentially important issue that requires solid confirmation in larger studies. By causing increased production of urine, diuretics may increase the urinary frequency.

Overactive bladder defined as a syndrome consisting of urgency, with or without incontinence, usually associated with nocturia, is common in older subjects treated with diuretics. Although often neglected by doctors, these symptoms may be troubling in elderly subjects.

Diuretics may cause several other adverse reactions, potentially leading to discontinuation. Hypokalemia was suggested as a potential trigger of arrhythmias and sudden cardiac death 60 , although its impact is now less than in the past because of the widespread use of low-dose thiazides, potassium-sparing diuretics, and combinations with ACE inhibitors or angiotensin receptor blockers.

Muscle cramps may cause suspicion of hypokalemia. Hyponatremia is another insidious side effect of diuretics and is particularly frequent in elderly women after prolonged use of the drug. Hyperuricemia is a dose-dependent effect that may lead to acute gouty arthritis.

Thiazide-type diuretics are at least as effective as β-blockers, calcium antagonists, and ACE inhibitors in reducing CV outcomes. Thiazide diuretics are particularly effective in preventing stroke and HF in hypertensive patients.

These drugs are very effective in the elderly and very elderly patients. The combined use of thiazide-like diuretics with aldosterone antagonists may be worthwhile.

Thus, diuretics should remain the leading agents in the management of hypertension. However, the statement that these drugs are superior to other drugs in almost all patients with hypertension is not supported by superiority studies.

Particularly in the younger hypertensive subjects, the benefit of diuretics as first-line antihypertensive drugs should be weight against the risk of unwanted effects in the long term.

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All other medications remained unchanged. Renal function decreased further, with eGFR of This decrease in renal function is most likely due to chlorthalidone. Thus dosage of chlorthalidone was reduced to Monday, Wednesday and Friday. Patient 3 — 64 year old African-American male was referred for uncontrolled hypertension and hypokalemia.

Laboratory results are shown in Table 1. Table 1: Patient 3 — Serial Blood Glucose Levels and HbA 1 c. He continued to take potassium chloride supplements. Thus it is safe to inform the patient that he does not have diabetes now but has a risk of developing diabetes in the future because of a high insulin response.

Patient 4 — 83 year old white male weighing pounds and with pre-existing congestive heart failure CHF , aortic stenosis, and aortic insufficiency with shortness of breath even with continuous oxygen therapy, and swelling of both lower extremities has been followed in the office of the corresponding author since the beginning of Intermittently, additional diuretics such as furosemide 20 to 40 mg daily and metolazone 2.

A laboratory has accompanied every office visit and serum glucose levels varied from normal to high, depending on the number of diuretics used, until when the glucose level remained consistently elevated.

In September of he was placed on glipizide 5mg PO with lunch and dinner, but glucose levels markedly increased despite discontinuing use of diuretic s. He was started on Glargine insulin, 25 units subcutaneously after breakfast and again after dinner.

Initiation of insulin treatment was followed by a steady decline of both FBG and 2hPPG to normal levels. His insulin dosage is reduced to 10 units after breakfast and dinner. In October of his HbA1c was 5.

Summary of his glucose levels in form of lows, highs, and mean levels from to are presented in Figure 3. Table 2: Patient 4 78y WM - HbA 1 c and Renal Function Parameters.

From Table 2 it should be noted that HbA1c is elevated until , when it is reduced to normal level concomitantly with decrease of glucose levels to normal after initiation of Glargine insulin therapy.

His renal function determined by serum creatinine is mildly impaired but it is non-progressive. He floridly responded to Glargine insulin with regression of hyperglycemia.

He feels well and maintains normal blood glucose levels FBG and 2hPPG with 10 units of glargine insulin twice daily. This study presents four patients who were treated with thiazide diuretic and developed hyperglycemia.

Two patients were treated with oral hypoglycemic agents and one with insulin detemir. Discontinuation of thiazide diuretic resulted in restoration of normoglycemia and termination of oral hypoglycemic agents. Diabetes in insulin treated patient Patient 2 could not be documented after discontinuation of insulin.

Authors observations indicate that hyperglycemia of variable severity is common in hypertensive patients treated with diuretics, mainly thiazide diuretics.

However, unlike other authors, these authors have demonstrated that hyperglycemia is reversible upon discontinuation of the diuretic as it is shown clearly in patient 3.

However, a patients' glucose level may not decrease upon discontinuation of the diuretic as in patient 4. This patient who has developed overt diabetes, requiring insulin therapy, raises an important question: does diureticinduced hyperglycemia lead to overt diabetes?

To that effect other authors have asked the question "are antihypertensive agents simply unmasking or masking diabetes" [ 6 ]? Intracellular potassium deficiency even with near normal serum potassium, is an important determining factor for hyperglycemia induced by diuretic therapy, and correction of hypokalemia using potassium supplements attenuates hyperglycemia [ 7 ].

Low serum potassium has been considered an important mechanism in the pathogenesis of diuretic induced hyperglycemia by these and other authors [ 6 , 7 ].

It is important to understand that serum potassium does not necessarily correlate with intracellular potassium stores. Therefore serum potassium may be normal but intracellular potassium deficit still persists and hence may attenuate endogenous insulin release and cause hyperglycemia.

Since it is difficult to measure intracellular potassium, we have to depend on serum potassium as an index of intracellular potassium. In patient 4 for example, serum potassium levels varied between 4.

He still developed sustained hyperglycemia with time leading to overt diabetes and required insulin therapy to control glucose levels.

A pearl of wisdom came from this patient where it was observed that control of persistent hyperglycemia with insulin therapy, markedly decreased his shortness of breath and he no longer requires oxygen therapy.

He is more lively than before. To that effect, it is important to seek out mechanisms other than hypokalemia alone to explain hyperglycemia. As such, other authors have identified HbA 1 c odd ratio 4.

The findings in our patient 4 concur with the previous observation. As shown in Table 2 , HbA 1 c in patient 4 increased from baseline 6. The problem of predicting cardiovascular or renal risk associated with drug-induced hyperglycemia still remains. There are several reasons for that: 1.

Diuretic, especially thiazide diuretic, is an essential therapy in hypertension and 2. Hypertension in and of itself is associated with much greater cardiovascular and renal risks thus making it difficult to distinguish them from those caused by diuretic therapy.

Most studies are post hoc findings and were not adequately powered to assess the association between diuretic therapy and new-onset diabetes [ 9 ]. New-onset diabetes was defined differently in different studies [ 9 ].

Further, comparing antihypertensive drug classes is difficult owing to differing study designs [ 10 ]. It is evident from all previous studies and our own observations that use of diuretics in the treatment of hypertension or CHF gives rise to hyperglycemia.

Thiazide diuretics such as HCTZ or chlorthalidone more often cause hyperglycemia than other diuretics. However, no prospective or long-term follow up studies are available to determine that diuretics merely cause hyperglycemia or unmask diabetes. Thus for now, diuretic-induced hyperglycemia is caused by volume and potassium depletion and treatment with potassium or reduction of the dose of diuretics reduce blood glucose levels to near normal or normal levels.

However, there are exceptions to this dictum. As such occasional patients with use of multiple diuretics may give rise to symptomatic diabetes requiring insulin therapy. Except for that, no microvascular or macrovascular complications, unique for untreated diabetes, have been observed in diuretic-induced hyperglycemia.

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However, subsequent post hoc analyses with validation of HF events and adjustment for pre-entry diuretic use seemed to confirm the original results Thus, ALLHAT did not meet its primary goal, and the evidence of superiority of chlortalidone over comparators was based on the analysis of secondary end points.

Furthermore, results obtained with chlorthalidone cannot be extrapolated to hydrochlorothiazide or other thiazide diuretics. The duration of the antihypertensive effect of chlorthalidone is significantly longer than that of hydrochlorothiazide, as evidenced by h ambulatory BP monitoring The results of ALLHAT are consistent with the INSIGHT study, which failed to detect outcome differences between a diuretic hydrochlorothiazide plus amiloride and a calcium antagonist nifedipine in a long-acting gastrointestinal transport system in 6, hypertensive patients aged 55—80 years.

Another major study that failed to demonstrate the superiority of diuretics over comparators was the ANBP2 trial. This was a randomized open-label study between diuretics and ACE inhibitors conducted in 6, elderly subjects with hypertension.

The ACE inhibitor enalapril and the diuretic hydrochlorothiazide were recommended as initial therapy, but the final choice of the specific agent was left to investigators, who were family practitioners. The primary end point of the study, a composite of CV morbidity and all-cause mortality, was marginally less frequent in the ACE inhibitor group than in the diuretic group hazard ratio [HR] 0.

ASCOT-BPLA Blood Pressure—Lowering Arm was a multicenter randomized controlled trial conducted in 19, hypertensive patients aged 40—79 years who had at least three other CV risk factors. Patients were randomized to a first-line treatment with either atenolol or amlodipine.

In the case of lack of BP control, bendroflumethiazide was added to atenolol and perindopril to amlodipine.

The trial was stopped prematurely after 5. The primary end point, a composite of nonfatal myocardial infarction and fatal CHD, did not differ between the groups HR 0.

Although the benefits of amlodipine and perindopril over atenolol and bendroflumethiazide appeared to be largely driven by the 2. The trial was prematurely stopped after a mean follow-up of 36 months because the boundary of the prespecified stopping rule was exceeded.

Also, the composite secondary end point death from CV causes, nonfatal myocardial infarction, and nonfatal stroke was less frequent in the benazepril-amlodipine group than in the benazepril-hydrochlorothiazide group HR 0.

These data may relegate thiazide diuretics to third-line therapy. However, since the study population was composed of complicated patients with hypertension and prior history of CHD, diabetes, or organ damage, it is unclear to what extent these findings can be extrapolated to less uncomplicated hypertensive subjects.

Diuretics increase the risk of NOD. In a network meta-analysis of 22 clinical trials, ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, and placebo were associated with a significantly lesser risk of NOD compared with diuretics The risk of NOD did not differ between diuretics and β-blockers Importantly, NOD was not a prespecified primary end point in any of these trials.

Diuretic-induced hypokalemia is believed to be one possible cause of the rise in glucose 52 , perhaps through an impaired insulin secretion by pancreatic β-cells. Also diuretic-induced hyperuricemia was associated with impaired glucose tolerance.

The controversy surrounding the issue of NOD in treated hypertensive subjects is not focused on the diabetogenic effect of diuretics and β-blockers, which is taken for granted 1 , but on the controversial interpretation of the few data on the prognostic impact of NOD induced by these drugs.

In a cohort study from our group, NOD portended a risk for subsequent CV disease that was not dissimilar from that of previously known diabetes. Notably, plasma glucose at entry and diuretic treatment at the follow-up visit were independent predictors of NOD Individuals who are skeptical about the adverse prognostic value of NOD argue that NOD failed to translate into a prognostic disadvantage in most trials.

In the ALLHAT study, the higher incidence of NOD in the chlorthalidone group did not translate into a prognostic burden in this group, and a similar situation occurred in other studies However, a frequently forgotten consideration is that different risks of NOD are unlikely to translate into different risks of hard end points in the setting of available mega-trials.

Consequently, even large trials such as ALLHAT may be under-powered to detect the adverse prognostic impact of NOD However, when the chlorthalidone, amlodipine, and lisinopril groups were analyzed separately, the excess risk of coronary artery disease was significant only in the lisinopril group HR 2.

The power of the chlorthalidone and amlodipine groups might have been inadequate to detect the adverse impact of NOD on coronary artery disease demonstrated in the total ALLHAT cohort.

We argued that the lesser BP reduction in the lisinopril group compared with the other groups might have allowed NOD to unveil its adverse prognostic impact In line with this interpretation, in a post hoc analysis of the SHEP study, NOD was associated with a higher risk of all-cause mortality HR 1.

Because the SHEP population was composed by elderly hypertensive patients at high risk of events in the short term, the favorable prognostic impact of BP reduction in the active treatment group may have outweighed the adverse prognostic impact of NOD.

In conclusion, we should refrain from underestimating the adverse prognostic impact of NOD induced by diuretics and β-blockers, alone or combined, solely because of the failure by most randomized trials to disclose a significant association between NOD and outcome.

NOD, whether or not induced by drugs, remains an important adverse prognostic marker that should be prevented. We suggested that in subjects at increased risk of NOD impaired fasting glucose, obesity, metabolic syndrome , diuretics and β-blockers should 1 be used cautiously, with the lowest effective dose and plasma glucose periodically checked, and 2 be avoided in subjects with BP normalized by different classes of antihypertensive drugs.

In a meta-analysis of studies 57 , diuretics increased cholesterol and triglyceride levels, and the rise in total cholesterol was paralleled by a rise in LDL cholesterol. The rise in cholesterol was dose dependent and greater in blacks.

A reduction in the HDL cholesterol levels was noted only in patients with diabetes. The potentially adverse prognostic impact of increased total and LDL cholesterol in the very long term may be underestimated by the relatively short duration generally 3—5 years of available intervention trials.

When dealing with a young hypertensive patient, it is unlikely that an expected persistent elevation of total and LDL cholesterol over decades may be beneficial.

The long-term use of diuretics was associated with an increased risk of renal cell carcinoma. In a meta-analysis, Grossman et al.

The renal tubular cells, which are the main target of diuretics, are also the site of origin of malignancy. The association between diuretic treatment and renal cell carcinoma is a potentially important issue that requires solid confirmation in larger studies.

By causing increased production of urine, diuretics may increase the urinary frequency. Overactive bladder defined as a syndrome consisting of urgency, with or without incontinence, usually associated with nocturia, is common in older subjects treated with diuretics. Although often neglected by doctors, these symptoms may be troubling in elderly subjects.

Diuretics may cause several other adverse reactions, potentially leading to discontinuation. Hypokalemia was suggested as a potential trigger of arrhythmias and sudden cardiac death 60 , although its impact is now less than in the past because of the widespread use of low-dose thiazides, potassium-sparing diuretics, and combinations with ACE inhibitors or angiotensin receptor blockers.

Muscle cramps may cause suspicion of hypokalemia. Hyponatremia is another insidious side effect of diuretics and is particularly frequent in elderly women after prolonged use of the drug.

Hyperuricemia is a dose-dependent effect that may lead to acute gouty arthritis. Thiazide-type diuretics are at least as effective as β-blockers, calcium antagonists, and ACE inhibitors in reducing CV outcomes.

Thiazide diuretics are particularly effective in preventing stroke and HF in hypertensive patients. These drugs are very effective in the elderly and very elderly patients. The combined use of thiazide-like diuretics with aldosterone antagonists may be worthwhile.

Thus, diuretics should remain the leading agents in the management of hypertension. However, the statement that these drugs are superior to other drugs in almost all patients with hypertension is not supported by superiority studies. Particularly in the younger hypertensive subjects, the benefit of diuretics as first-line antihypertensive drugs should be weight against the risk of unwanted effects in the long term.

This holds particularly true in subjects at high risk of developing diabetes. This publication is based on the presentations at the 3rd World Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension CODHy. The Congress and the publication of this supplement were made possible in part by unrestricted educational grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Ethicon Endo-Surgery, Generex Biotechnology, F.

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We are sorry that this post was not useful for you! Let us improve this post! Tell us how we can improve this post? Submit Feedback. can diuretics increase blood sugar Diuretics Affect Blood Sugar Levels diuretics and diabetes how diuretics cause hyperglycemia. Shahana Khatoon. Subsequently, he became hypertensive and was treated with a thiazide diuretic but no antidiabetic agents.

He then developed new-onset diabetes. Results: All patients showed hyperglycemia above FBG criteria for diabetes. Two patients were prescribed antidiabetic therapy which was stopped with no worsening of hyperglycemia although diuretic therapy continued.

In two patients diuretic was discontinued. Hyperglycemia abated in one, while in the other, hyperglycemia worsened requiring Glargine insulin. Conclusion : Hyperglycemia is common in patients with hypertension or CHF treated with a thiazide diuretic alone or in combination with other diuretics.

It may be more appropriate to define elevated glucose associated with diuretic "hyperglycemia" rather than new-onset diabetes. The real issue is that use of thiazide diuretics is imperative in blood pressure control especially in resistant hypertension.

Even with new-onset diabetes, thiazide diuretics are commonly found to be safe, reducing risk of stroke, heart attack, and renal failure characteristic of uncontrolled hypertension.

Therefore, risks of new-onset diabetes, induced by diuretic therapy, will be difficult to ascertain because of hypertension for which thiazide diuretic is widely used. Diabetes is a major cardiovascular risk factor, but drug-induced new-onset diabetes may not have clinical significance and should not be a major determinant when choosing a treatment for hypertension if the medication is necessary to reduce blood pressure[ 1 ].

A study found no difference in the number of patients who developed diabetes with different antihypertensive drugs, including diuretics and beta blockers as shown in Figure 1 [ 2 ]. Figure 1: Risk of hyperglycemia in patients receiving antihypertensive drugs. ACE — angiotensin converting enzyme; ORs-odds ratios; CIsconfidence intervals.

Adapted from Gurwitz,J. et al. Ann Intern Med ; [ 2 ]. Figure 1 demonstrates that all antihypertensive drugs may produce hyperglycemia although the risk of hyperglycemia varies.

The investigators concluded that "there was no advantage to the use of Lisinopril compared with a diuretic despite the difference in new-onset diabetes". The use of alpha blockers does not increase serum glucose; but in the ALLHAT study, cardiovascular events were more frequent with an alpha blocker compared with a diuretic [ 3 ].

A group of investigators from Italy studied the outcome of new-onset diabetes in treated hypertensive subjects compared to those with previously known diabetes.

They found that subjects in whom diabetes developed were exposed to diuretics, calcium channel blockers, and angiotensin converting enzyme inhibitors ACEI more frequently than those in whom diabetes did not develop as shown in Figure 2 [ 4 ].

Figure 2: Distribution of antihypertensive treatments at the follow-up visit in nondiabetic subjects, subjects with newonset diabetes, and subjects with previously known diabetes. Adapted from Verdcchia P, et al. Hypertension ; [4]. The purpose of this communication is to present a few patients who were diagnosed to have developed diabetes during treatment of hypertension who were then placed on antidiabetic therapy.

Withdrawal of antidiabetic therapy and treatment with potassium supplements did not result in worsening of hyperglycemia or appearance of overt diabetes. In addition, a patient is presented to demonstrate that diureticinduced hyperglycemia may occasionally lead to overt diabetes requiring insulin therapy.

Hyperglycemia or new-onset diabetes has not been clearly defined. Patient 1 — A 67 year old African American male was referred by a primary care physician and seen by the authors AKM in the office in November of for renal insufficiency.

He gave history of hypertension for a long time and diabetes for nine months. He is a farm worker and is very active. Daily medication at the time of first visit consisted of hydrochlorothiazide HCTZ 25 mg, glimepiride 2 mg, Lisinopril 40 mg, pravastatin 80 mg, amlodipine 10 mg, metoprolol mg, and allopurinol mg all PO daily.

Otherwise his physical examination was normal. Action at this office visit included discontinuation of Lisinopril, increase of amlodipine to 10 mg a. and 5 mg p. to improve BP control, and decrease of allopurinol mg due to decreased kidney function , and decrease of pravastatin to 40 mg PO daily.

Fasting and 2-h basic metabolic panel BMP , glycosylated hemoglobin HbA1c and serum insulin levels were ordered. Both of these levels were normal. The 2hPP serum insulin level was At this time, he was advised to discontinue glimepiride, switch HCTZ to chlorthalidone 25 mg daily, increase amlodipine to 10 mg twice daily, and potassium chloride 20 mEq daily was added.

At his third visit, six weeks later, his glucose levels for both FBG and 2 hPPG were increased. He returned to the office in late March of with a laboratory done March 1, His fasting insulin was normal Thus potassium intake was increased to 20 mEq twice daily and the patient was advised to increase dietary potassium.

Thus here is a patient who went to a physician for treatment of hypertension. He was treated with a thiazide diuretic, beta blocker, calcium channel blocker and ACEI drugs.

All of these antihypertensive drugs have been documented to produce hyperglycemia Figure 1 [ 1 , 2 ]. Thus he was labeled to have developed Type 2 diabetes mellitus DM and placed on glimepiride, an oral hypoglycemic agent. Perhaps the primary care physician did not know that it is common to find hyperglycemia when a patient is treated with a thiazide diuretic, and glucose level is often reduced with correction of serum potassium.

BP is under control and kidney function is improving. This slightly elevated glucose is clearly due to the thiazide diuretic, chlorthalidone, as evidenced by concomitant hypokalemia. His major risk factors were uncontrolled hypertension which is now under control, and decreased kidney function which is now improving.

He is asymptomatic and active. Patient 2 — A 58 year old white male, wheelchair bound, a self-referral to AKM in November of , gave an 8 to 10 ten year history of diabetes. He was treated with metformin mg PO twice daily, glipizide 5 mg PO daily, enalapril 10 mg PO daily, indomethacin 50 mg PO every 8 hours for gout, and Lipitor 10 mg PO daily.

The patient was also diagnosed with atrial fibrillation which was treated with digoxin 0. Two months prior to the first office visit with this author, the patient was admitted to a local hospital with acute renal failure where oral hypoglycemic agents were discontinued and he was started on insulin.

At the time of the first office visit, the patient was receiving insulin detemir Levemir ® 20 U subcutaneously at bedtime, warfarin with dose adjusted according to INR, allopurinol mg PO daily, metoprolol 25 mg PO BID, and sodium bicarbonate mg PO TID.

His urinalysis was normal.