Daniel L. Gallina

Patient adherence improves glycemic control

Purpose The purpose of this study was to assess the influence of appointment keeping and medication adherence on HbA1c. Methods A retrospective evaluation was performed in 1560 patients with type 2 diabetes who presented for a new visit to the Grady Diabetes Clinic between 1991 and 2001 and returned for a follow-up visit and HbA1c after 1 year of care. Appointment keeping was assessed by the number of scheduled intervening visits that were kept, and medication adherence was assessed by the percentage of visits in which self-reported diabetes medication use was as recommended at the preceding visit. Results The patients had an average age of 55 years, body mass index (BMI) of 32 kg/m2, diabetes duration of 4.6 years, and baseline HbA1c of 9.1%. Ninety percent were African American, and 63% were female. Those who kept more intervening appointments had lower HbA1c levels after 12 months of care (7.6% with 6-7 intervening visits vs 9.7% with 0 intervening visits). Better medication adherence was also associated with lower HbA1c levels after 12 months of care (7.8% with 76%-100% adherence). After adjusting for age, gender, race, BMI, diabetes duration, and diabetes therapy in multivariate linear regression analysis, the benefits of appointment keeping and medication adherence remained significant and contributed independently; the HbA1c was 0.12% lower for every additional intervening appointment that was kept (P= .0001) and 0.34% lower for each quartile of better medication adherence (P= .0009). Conclusion Keeping more appointments and taking diabetes medications as directed were associated with substantial improvements in HbA1c. Efforts to enhance glycemic outcomes should include emphasis on these simple but critically important aspects of patient adherence.

Clinical Inertia Contributes to Poor Diabetes Control in a Primary Care Setting

Purpose The purpose of this study was to determine whether “clinical inertia”—inadequate intensification of therapy by the provider—could contribute to high A1C levels in patients with type 2 diabetes managed in a primary care site. Methods In a prospective observational study, management was compared in the Medical Clinic, a primary care site supervised by general internal medicine faculty, and the Diabetes Clinic, a specialty site supervised by endocrinologists. These municipal hospital clinics serve a common population that is largely African American, poor, and uninsured. Results Four hundred thirty-eight African American patients in the Medical Clinic and 2157 in the Diabetes Clinic were similar in average age, diabetes duration, body mass index, and gender, but A1C averaged 8.6% in the Medical Clinic versus 7.7% in the Diabetes Clinic (P < .0001). Use of pharmacotherapy was less intensive in the Medical Clinic (less use of insulin), and when patients had elevated glucose levels during clinic visits, therapy was less than half as likely to be advanced in the Medical Clinic compared to the Diabetes Clinic (P < .0001). Intensification rates were lower in the Medical Clinic regardless of type of therapy (P < .0001), and intensification of therapy was independently associated with improvement in A1C (P < .001). Conclusions Medical Clinic patients had worse glycemic control, were less likely to be treated with insulin, and were less likely to have their therapy intensified if glucose levels were elevated. To improve diabetes management and glycemic control nationwide, physicians in training and generalists must learn to overcome clinical inertia, to intensify therapy when appropriate, and to use insulin when clinically indicated.

Diabetes in Urban African-Americans: II. High prevalence of microalbuminuria and nephropathy in African-Americans with diabetes

OBJECTIVE African-Americans with diabetes have an increased risk of endstage renal disease, but underlying mechanisms are poorly understood. We undertook this study to evaluate prevalence and risk factors for renal disease in an African-American population with diabetes. RESEARCH DESIGN AND METHODS We measured urine albumin excretion in 578 consecutive patients presenting for the first time to the Grady Memorial Hospital Diabetes Unit in Atlanta, GA. The unit serves an urban population that is predominantly African-American; 85% of patients have non-insulin-dependent diabetes mellitus (NIDDM). Subjects provided 24-h and/or ∼ 3-h urine collections for measurement of albumin and creatinine. RESULTS Correlation of the albumin/creatinine ratio (μg/mg) with the 24-h albumin excretion rate was 0.89 (P < 0.001, n = 123). Although the median duration of diabetes was only 1 year, among all subjects, the estimated prevalence of microalbuminuria (30–300 mg albumin/24 h) was 25% and that of nephropathy (> 300 mg albumin/24 h) was 11%. Among African-Americans with NIDDM (n = 466), the estimated prevalence of microalbuminuria was 24% and that of nephropathy was 12% prevalence remained high (25 and 5%, respectively) among 219 patients with < 1 year known duration of diabetes. Metabolic control was not associated with disease. However, among all subjects with NIDDM, the odds ratio for nephropathy among subjects with disease duration > 5 years compared with those with disease duration < 1 year was 4.65 (95% confidence interval [CI] 2.24–9.79), and the odds ratio for nephropathy among subjects with hypertension compared with those without hypertension was 2.64 (CI 1.42–4.93). Odds ratios were comparable among African-Americans with NIDDM. Trends were similar but less significant for subjects with microalbuminuria. CONCLUSIONS Albuminuria can be identified reliably and conveniently by the albumin/creatinine ratio in brief urine collections. In our patients, clinically significant albuminuria occurred in 36% of persons at first presentation. Since increased risk was associated with hypertension and control of hypertension can slow progression of renal disease, screening for albuminuria and treatment of hypertension should be aggressive in urban populations of African-Americans with diabetes.

Diabetes in Urban African-Americans. IX. Provider Adherence to Management Protocols

OBJECTIVE Staged diabetes management should permit glycemic goals to be attained in a timely manner, but the success of such an approach requires conformity by health care providers. To test performance, we analyzed the adherence of practitioners to a protocol for staged management of NIDDM patients. RESEARCH DESIGN AND METHODS Records of patients treated at the Grady Memorial Hospital Diabetes Clinic were reviewed retrospectively over a 3-year period. For each patient, intensification of therapy was indicated if fasting plasma glucose was > 7.8 mmol/l and a prior HbA1c was > 7.0%. Protocols dictated a progression from dietary therapy alone to increasing dosages of sulfonylureas to increasing dosages of insulin. Patients were seen at bimonthly intervals. RESULTS During the 3-year period, 1,051 patient visits met protocol criteria for intensification. Adherence to the protocol improved significantly in the 3rd year compared with the first 2 years (30, 31, and 47% adherence in the 1st, 2nd, and 3rd years, respectively). Patients treated with diet alone were significantly less likely to have their therapy intensified than patients on sulfonylureas or insulin (intensification rates 25, 41, and 47%, respectively). In the management of patients treated with diet alone, practitioners were reluctant to intensify therapy at early visits, but were more likely to do so later, 19% of patients beyond goal range at the 2-month visit were started on pharmacological therapy vs. 28% at the 4-month visit, and 39% at the 6-month visit (P < 0.01). In contrast, there was no significant difference in the frequency of therapy intensification between early and late visits for patients on sulfonylureas or insulin. Practitioners appeared to base the decision to intensify on the fasting plasma glucose level more than on the most recent HbA1c. Age did not appear to be a significant factor in the decision to intensify. CONCLUSIONS Although staged management protocols constitute critical tools to achieve glycemic goals, the adherence of health care providers may be suboptimal. Special efforts may be needed to assure compliance.

Hypercalcemia in hyperthyroidism: patterns of serum calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D3 levels during management of thyrotoxicosis.

OBJECTIVE To present two cases of hypercalcemia associated with thyrotoxicosis and to describe serial biochemical findings during the course of treatment of hyperthyroidism. METHODS We report two cases, illustrate the changes in serum calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D3 levels during management of thyrotoxicosis, and compare our findings with those in previous studies. RESULTS Hypercalcemia attributable to thyrotoxicosis is well documented, but the mechanism for the hypercalcemia is incompletely understood. Our first patient had a complicated medical history and several potential causes of hypercalcemia, including recurrent hyperparathyroidism, metastatic breast cancer, and relapse of previously treated thyrotoxicosis. A suppressed parathyroid hormone level and negative bone and computed tomographic scans excluded the first two factors. After thyroid ablation with 131I, the serum calcium and thyroxine levels decreased, and the parathyroid hormone and 1,25-dihydroxyvitamin D3 levels normalized. Our second patient, who was referred to our institution with a preliminary diagnosis of hypercalcemia associated with malignant disease and who had no symptoms of hyperthyroidism, was found to have a high free thyroxine level, diffuse enlargement of the thyroid, and high uptake (58%) of 123I on a thyroid scan. After thyroid ablation, the serum calcium, 1,25-dihydroxyvitamin D3, and intact parathyroid hormone levels normalized, and the free thyroxine level declined. The probable pathogenesis of hypercalcemia in thyrotoxicosis is reviewed with respect to thyroid hormone and its effect on bone turnover. CONCLUSION Physicians should consider thyrotoxicosis in the differential diagnosis of hypercalcemia.

Diabetes in urban african americans. III. Management of type II diabetes in a municipal hospital setting

OBJECTIVE Management of type II diabetes is difficult, particularly in urban populations with limited resources and access to care. To evaluate the effectiveness of structured care delivered by non-physician providers, patients were studied prospectively for 6 months in a municipal hospital diabetes clinic. DESIGN AND METHODS The population was approximately 90% African American and had median known diabetes duration of approximately 1 year, 54% had incomes below the Federal Poverty Guideline. Primary management was provided by nurse-practitioners and dietitians, and primary outcome measures were hemoglobin A1c (HbA1c), fasting plasma glucose, and changes in body weight. RESULTS Responses were analyzed in 325 new patients returning for visits at 2, 4, 6, and 12 months; metabolic profiles at presentation were similar to those of subjects who missed intervening visits. Lean patients largely continued on pharmacologic therapy and improved HbA1c from 9.4% to 7.4% at 2 months (P < 0.001), remained stable through 6 months, then rose to 7.9% at 1 year. Obese patients (71%) received dietary instruction. Weaning of pharmacologic therapy was attempted for the first 2 months, resulting in a decline of HbA1c from 9.6% to 8.0% (P < 0.001), with 70% treated with diet alone. In the obese, HbA1c continued to decrease through 6 months (7.7%). Thereafter, providers saw patients at their own discretion and intensified therapy as needed. Although by 1 year, HbA1c had risen to only 8.2%, some patients required reinstitution of pharmacologic therapy; 59% were on diet alone. While 52% lost 4 lb or more (mean 9.3) by 2 months, little additional weight was lost. Interestingly, glycemic control was improved both in those who lost > or = 8.5 lb in the first 2 months (HbA1c 9.6% to 8.1% at 12 months), and in those who gained weight (HbA1c 10.2% to 8.2%). In the obese patients using pharmacologic agents at presentation, 35% were able to discontinue oral agents or insulin by 1 year, with good glycemic control (HbA1c < 8%). For patients who were initially on diet alone, a fasting plasma glucose > 177 mg/dL predicted the need for pharmacologic therapy with 97% certainty. CONCLUSIONS In urban African American patients, nonpharmacologic management of type II diabetes substantially improves metabolic control; decreases in HbA1c are comparable in those who do and do not lose weight. Therapy managed by nonphysician providers can be an effective cornerstone of diabetes care in this socioeconomically disadvantaged population.

The Improving Primary Care of African Americans with Diabetes (IPCAAD) project: rationale and design

African Americans have an increased burden of both diabetes and diabetes complications. Since many patients have high glucose levels novel interventions are needed, especially for urban patients with limited resources. In the Grady Diabetes Clinic in Atlanta, a stepped care strategy improves metabolic control. However, most diabetes patients do not receive specialized care. We will attempt to translate diabetes clinic approaches to the primary care setting by implementing a novel partnership between specialists and generalists. We hypothesize that endocrinologist-supported strategies aimed at providers will result in effective diabetes management in primary care sites, and the Improving Primary Care of African Americans with Diabetes project will test this hypothesis in a major randomized, controlled trial involving over 2000 patients. Physicians in Grady Medical Clinic units will receive (1) usual care, (2) computerized reminders that recommend individualized changes in therapy and/or (3) directed discussion by endocrinologists providing feedback on performance. We will measure outcomes related to both microvascular disease (HbA1c, which reflects average glucose levels over an approximately 2-month period) and macrovascular disease (blood pressure and lipids) and assess provider performance as well. We will compare two readily generalizable program interventions that should delineate approaches effective in a primary care setting as needed to improve care and prevent complications in urban African Americans with type 2 diabetes.

High Prevalence of Albuminuria Among African-Americans With Short Duration of Diabetes

These two conditions are considered variants of the same defect of the stimulatory guanine nucleotide-binding (Gs) protein of adenylate cyclase, which is necessary for parathyroid hormone and other hormones such as gonadotropin, beta-adrenergic agonist, and thyrotropin to use cAMP as an intracellular second messenger. We described two related women with apparent AHO and late-onset diabetes. Both patients had normal serum calcium levels, normal parathyroid hormone levels, and the characteristic somatic features of short stature, round face, obesity, and shortened fourth and fifth metacarpals and metatarsals, consistent with pseudo-PHP Both disorders, PHP and pseudo-PHP, can occur within the same family, and there is accumulating evidence that genomic imprinting is involved in the disease (1). Full phenotypic expression (AHO and parathyroid hormone resistance, as in PHP type la) occurs in maternally transmitted cases, whereas partial expression (AHO without parathyroid hormone resistance, as in pseudo-PHP) occurs when the gene is paternally transmitted. The pedigree of our patients showed genetic transmission from their father. Patients with type 2 diabetes have defects in insulin action, abnormal insulin secretion, and increased hepatic glucose production. Although precise pathways responsible for these defects have not been thoroughly identified, they are likely to be genetically heterogenous with mutations in several different genes that are able to cause hyperglycemia. Some reported genetic loci for type 2 diabetes have been mapped on chromosome 20q, chromosome 7p, chromosome 12q, chromosome 2, and so forth (2,3). In most cases of AHO, reduced levels of Gs protein a subunit (Gsa protein) have been found. A number of deactivating mutations in the gene for Gsa protein located on chromosome 20ql3 have been described for this disorder (1), but del(2)(q37) has also been described in some AHO patients (4) and thus explains the heterogeneity observed in this AHO disorder. PHP type la or pseudo-PHP is assumed to be a Gsa protein problem and this protein is encoded by chromosome 20ql3. 2-3. Occasionally, these disorders may be associated with resistance of diverse target tissues to hormones and neurotransmitters whose actions require stimulation of adenylate cyclase and thus open calcium channels. It should be considered whether this Gsa protein problem will lead to diabetes with insulin resistance. Certainly, either these pseudo-PHP women with type 2 diabetes have a mutation in the Gsa protein or nearby genome for its susceptibility to type 2 diabetes, or they represent just a phenomenon of coincidence. Further evaluation and collection of cases are necessary to define the possible role and interrelationship of pseudo-PHP and type 2 diabetes.

Diabetes in Urban African Americans: Assessment of Diabetes-Specific Locus of Control in Patients With Type 2 Diabetes:

PURPOSE This study was conducted to examine the applicability and relationship to glycemic control of the Diabetes Locus of Control (DLC) Scales in a low-literacy, economically deprived, African American population with type 2 diabetes. METHODS The DLC Scales were administered orally to African American patients with type 2 diabetes who had been referred to the diabetes unit of a large urban public hospital. Reliability, interscale correlations, and associations with patient characteristics were compared with those originally obtained for a better educated, predominately Caucasian population. RESULTS The structure and correlates of the DLC Scales in the African American population were more similar than different from those originally obtained from a primarily well-educated, Caucasian population. However, comprehension of some items was difficult for up to 10% of the low-literacy population. A significant relationship was found between belief in chance and both glycemic control at the 6-month follow-up and the change in glycemic control over time. CONCLUSIONS Although the DLC Scales operate similarly in an urban African American population with limited education, further modification is needed to enhance the prediction of glycemic control and provide direction for developing targeted interventions.

Use of a Glucose Algorithm to Direct Diabetes Therapy Improves A1C Outcomes and Defines an Approach to Assess Provider Behavior

Purpose The purpose of this study was to determine whether an algorithm that recommended individualized changes in therapy would help providers to change therapy appropriately and improve glycemic control in their patients. Methods The algorithm recommended specific doses of oral agents and insulin based on a patients medications and glucose or A1C levels at the time of the visit. The prospective observational study analyzed the effect of the algorithm on treatment decisions and A1C levels in patients with type 2 diabetes. Results The study included 1250 patients seen in pairs of initial and follow-up visits during a 7-month baseline and/or a subsequent 7-month algorithm period. The patients had a mean age of 62 years, body mass index of 33 kg/m2, duration of diabetes of 10 years, were 94% African American and 71% female, and had average initial A1C level of 7.7%. When the algorithm was available, providers were 45% more likely to intensify therapy when indicated (P = .005) and increased therapy by a 20% greater amount (P < .001). A1C level at follow-up was 90% more likely to be <7% in the algorithm group, even after adjusting for differences in age, sex, body mass index, race, duration of diabetes and therapy, glucose, and A1C level at the initial visit (P < .001). Conclusions Use of an algorithm that recommends patient-specific changes in diabetes medications improves both provider behavior and patient A1C levels and should allow quantitative evaluation of provider actions for that providers patients.