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PubMed2004

Comparison of fluvastatin + fenofibrate combination therapy and fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus, and coronary heart disease: a 12-month, randomized, double-blind, controlled trial.

BACKGROUND: Diabetes risk is often complicated by a mixed hyperlipoproteinemia not sufficiently controlled by a single antihyperlipidemic drug; however, there are some concerns about the safety of combined statin and fibrate treatments. OBJECTIVE: The aim of this study was to compare the efficacy and safety profile of fluvastatin + fenofibrate combination therapy and those of fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus (DM), and coronary heart disease (CHD) (ie, high risk for cardiovascular disease [CVD]). METHODS: This 12-month, randomized, double-blind, controlled trial was conducted at the University of Pavia, Pavia, Italy. Patients aged 18 to 80 years with combined hyperlipidemia, type 2 DM, and CHD were randomly assigned to receive combination therapy with extended-release fluvastatin 80 mg + micronized fenofibrate 200 mg or monotherapy with extended-release fluvastatin 80 mg. All treatments were given in tablet form, once daily with the evening meal, for 12 months. Lipid variables (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) at 6 and 12 months were the primary efficacy variables, and glycemic status (glycosylated hemoglobin [HbA(1c)], fasting plasma glucose, and postprandial plasma glucose levels) at 6 and 12 months was the secondary efficacy variable. Tolerability was assessed using physical examination, including vital-sign assessment, body-weight measurement, electrocardiography, adverse events, and laboratory tests. A pharmacoeconomic analysis of both treatment regimens was also carried out using the incremental cost-effectiveness ratio (ICER). RESULTS: A total of 48 patients (24 men, 24 women; mean [SD] age, 60 [5] years) were enrolled. After 6 months, all primary efficacy variables, except for TG level, showed significant improvements from baseline only in the combination-therapy group (changes: LDL-C, -25%; HDL-C, +12%; and TC, -19%; all, P < 0.05 vs baseline). After 12 months, lipid variables showed significant improvements over baseline in both groups (all, P < 0.05), except for TG in the monotherapy group. Significant changes in LDL-C, HDL-C, and TG were found in the combination-therapy group (-35%, +34%, -32%, respectively) versus the monotherapy group (-25%, +14%, -17%, respectively; all, P < 0.05 between groups). The change from baseline in HbA(1c) level was significant with combination therapy (-12% vs -7%; P < 0.05). Both treatments were well tolerated, with no significant differences in the incidences of adverse events between the 2 groups. The ICER showed that each 1% decrease in LDL-C level achieved with the fenofibrate + fluvastatin combination added a cost of 14.97 Euros/y (US 12.25 US dollars/y), and each 1% increase in HDL-C level added a cost of 7.48 Euros/y (6.12/y US dollars), over the cost of monotherapy. CONCLUSIONS: In this selected sample of patients with combined hyperlipidemia, type 2 DM, and CHD, the combination of extended-release fluvastatin + micronized fenofibrate was associated with a more improved lipid profile than fluvastatin monotherapy, and was a well-tolerated and cost-effective therapeutic choice to treat these patients at high risk for CVD.

Adolescent↗
PubMed2001

Treating obesity in youth: should dietary glycemic load be a consideration?

Although the adverse effects of excess adiposity on health outcomes are widely recognized, there is no consensus regarding the most appropriate dietary strategies for managing obesity in youth. Recently, a novel dietary variable termed glycemic load has been postulated to influence hunger and body weight regulation. Glycemic load, a measure of the effects of a meal on blood glucose levels, is determined by the type and the amount of carbohydrate consumed. According to a hypothetical model, ingestion of high-glycemic load meals induces a sequence of hormonal changes that alter partitioning of metabolic fuels, exacerbate hunger, and over the long-term, promote weight gain. This chapter provides an overview of the available evidence suggesting that dietary glycemic load, and its related factor, the glycemic index, should be taken into consideration in the design of weight loss interventions.

Adolescent↗
PubMed1994

[Health and factors associated with glycemic control in 165 children with insulin-dependent diabetes, aged 7-23 year].

BACKGROUND: A multicenter cross-sectional study was the first step of a project aimed at performing an educational diagnosis for IDDM children in France. POPULATION AND METHODS: Inclusion criteria were age 7 to 13 years, IDDM duration > 6 months and to be followed in a university pediatric department. One hundred and seventy-three children, followed in six centers, were eligible. One hundred and sixty-five of them (age 10.2 +/- 1.9 years and IDDM duration 3.1 +/- 2.7 years) agreed to participate. Standardized questionnaires were completed by the parents and children. Clinical examination was performed and a medical questionnaire was completed by the usual diabetologist of children. HbA1c was measured using a single HPLC method (normal levels +/- 2 sd = 4.5 to 5.7%). RESULTS: Mean HbA1c was 8.3 +/- 1.6% (range 5-13.2%) and values were distributed as follows: < or = 7% for 24.5%, < or = 8% for 46.6% and > 10% for 14% of the children. Age (r = 0.33, P < 0.001), duration of diabetes (r = 0.29, P < 0.001), number of biochemical hypoglycemias (r = -0.21, P < 0.01) and cholesterol level (r = 0.31, P < 0.001) were correlated with HbA1c levels and accounted for 30% of the variance in predicting HbA1c. The difference of HbA1c levels between prepubertal and pubertal children was significant (P < 0.02). Other usual clinical parameters as well as indexes for diabetes monitoring were not significantly correlated with HbA1c. In addition, four subgroups were associated with a significant deterioration (delta > or = 1%) in mean HbA1c levels: 1) age > 10 years (n = 82, P < 0.01); 2) pubertal stage in girls (Tanner stages III vs I, P < 0.05); 3) IDDM duration > or = 2 years (n = 106, P < 0.001); 4) a non French native mother (n = 27, P < 0.001). CONCLUSIONS: Only 50% of this group under specialized care had an acceptable level of glycemic control (HbA1c < or = 8%). Factors related to glycemic control were identified, as well as subgroups of children at particular risk for bad glycemic control which requires specifically targeted interventions. The analyse of sociodemographic, psychological, familial and cognitive factors is currently being conducted in this population, in order to find other explicative variables of glycemic control and to develop specifically targeted educational programs.

Adolescent↗
PubMedDate not supplied

Role of self-monitoring of blood glucose in glycemic control.

OBJECTIVE: To examine the role of self-monitoring of blood glucose (SMBG) in the management of diabetes mellitus. METHODS: Current trends and published evidence are reviewed. RESULTS: Despite the widespread evidence that lowering glycemic levels reduces the risks of complications in patients with diabetes, little improvement in glycemic control has been noted among patients in the United States and Europe in recent years. Although SMBG has been widely used, considerable controversy surrounds its role in achieving glycemic control. The high cost of test strips has made considerations regarding appropriate recommendations for SMBG a priority, especially in light of the current climate of health-care cost-containment. Existing clinical recommendations lack specific guidance to patients and clinicians regarding SMBG practice intensity and frequency, particularly for those patients not treated with insulin. Previous studies of the association between SMBG and glycemic control often found weak and conflicting results. CONCLUSION: A reexamination of the role of SMBG is needed, with special attention to the unique needs of patients using different diabetes treatments, within special clinical subpopulations, and during initiation of SMBG versus its ongoing use. Further understanding of the intensity and frequency of SMBG needed to reflect the variability in glycemic patterns would facilitate more specific guideline development. Educational programs that focus on teaching patients the recommended SMBG practice, specific glycemic targets, and appropriate responses to various blood glucose readings would be beneficial. Continuing medical education programs for health-care providers should suggest ways to analyze patient SMBG records to tailor medication regimens. For transfer or communication of SMBG reports to the clinical staff, a standardized format that extracts key data elements and allows quick review by health-care providers would be useful. Because the practice of SMBG is expensive, the cost-effectiveness of SMBG needs to be carefully assessed.

Blood Glucose↗
PubMed1990

Glycemic index of foods in individual subjects.

We studied 12 subjects with diabetes to determine how well the glycemic index (GI) predicted the ranking of glycemic responses of different foods in individuals. All subjects ate three mixed meals (bread, rice, or spaghetti with GIs of 100, 79, and 61, respectively) four times in a randomized complete block design. The mean glycemic response areas of the different meals ranked according to the predicted GI in every individual. The observed mean +/- SD GI values of the meals were significantly different from each other (bread 100 +/- 7, rice 75 +/- 9, spaghetti 54 +/- 9), with no significant difference in response between subjects. It is concluded that individuals share common mean GI values for different foods. Within confidence limits determined by the variability of glycemic responses, the number of repeated tests conducted, and the expected GI difference, the GI can be used to predict the ranking of the mean glycemic responses of mixed meals taken by individuals.

Adult↗
PubMedDate not supplied

Insulin analogues in the management of diabetes.

Insulin therapy has been strongly influenced by the results of the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS), both of which support intensive antidiabetic therapy. Conventional insulin therapy can be limited, due to the difficulty in achieving tight glycemic control in people with diabetes, which is crucial to reducing the risk of long-term complications associated with diabetes. In recent years, three short-acting (insulin lispro, insulin aspart and insulin glulisine) and two long-acting (insulin glargine and insulin detemir) recombinant analogues of regular human insulin have been developed for the management of diabetes. Short-acting insulin analogues are an alternative to regular human insulin before meals. Compared with regular human insulin, these new short-acting insulin analogues show faster subcutaneous absorption, a more rapid onset of activity and a shorter duration of action. As a result of these pharmacokinetic differences, an improved postprandial glycemic control is achieved, without increasing the risk of hypoglycemia. In addition, these insulin analogues can be administered immediately before a meal, thereby synchronizing insulin administration and food absorption. The long-acting insulin analogue insulin glargine was developed to provide basal insulin levels for 24 h when administered once daily at bedtime. Compared with previous intermediate- or long-acting conventional insulin, insulin glargine shows a flat profile of plasma insulin levels with no prominent peak. The use of this long-acting insulin analogue appears to be associated with a reduced incidence of hypoglycemia, especially at night. Insulin detemir is another basal insulin that may reduce nocturnal hypoglycemia and variability in glycemic values. The availability of these new insulin analogues has the potential to significantly improve long-term control over blood glucose in diabetic patients.

Amino Acid Sequence↗
PubMed1993

Effect of war-induced prolonged stress on cortisol of persons with type II diabetes mellitus.

The study was designed to assess the impact of protracted, war-induced stress on cortisol levels and glycemic control in persons with Type II diabetes mellitus. A randomly selected sample of 44 displaced Type II diabetic persons was compared with a group of diabetic persons matched for sex, age, weight, duration of diabetes, and type of treatment who had not been forced to leave their homes. The self-reported stress, depression level, serum cortisol, fasting blood glucose, and glycosylated hemoglobin were compared. The two groups were found to be significantly different in scores for self-reported stress and depression level. Passive coping patterns prevailed in the displaced group. The serum cortisol levels correlated positively with self-reported stress, negatively with active coping patterns, and were significantly higher in the displaced persons group. No significant differences were found between the group on the variables measuring glycemic control. The results indicate that prolonged stress need not worsen glycemic control in Type II diabetic patients.

Adaptation, Psychological↗
PubMed1987

The glycemic index: similarity of values derived in insulin-dependent and non-insulin-dependent diabetic patients.

To see whether relative differences in the glycemic responses to different foods were similar in insulin-dependent (IDDM) and non-insulin-dependent diabetic patients (NIDDM) we determined the glycemic index (GI) of a total of 20 foods and mixed test meals in groups of IDDM and NIDDM volunteers. The mean GI values ranged from 32 in NIDDM and 41 in IDDM (pearled barley) to 105 in NIDDM and 111 in IDDM (bread with cheese and tomato). The correlation between the mean GI values in IDDM and NIDDM was highly significant (r = 0.927, p less than 0.001). The mean GI values for 15 of the 20 test meals was greater in IDDM than in NIDDM (mean of GI for all 20 foods, 76 in IDDM compared with 68 in NIDDM, p less than 0.005). However, the difference in GI between IDDM and NIDDM was t statistically significant for 19 of the 20 individual test meals. Greater within-individual variability of glycemic responses in IDDM probably accounts for the slightly greater mean GI value seen in IDDM compared with NIDDM. The addition of 32 g cheddar cheese to four foods which were also fed without cheese had no significant effect on the GI in NIDDM (mean GI of 68 without cheese compared with 72 for the meals with cheese), but had a small effect in IDDM where the mean GI was increased from 72 to 87 (p less than 0.05). However, despite small increases in glycemic response to foods with added cheese, the relative differences between foods were unaffected by the addition of cheese in both IDDM and NIDDM. It is concluded that mean GI values for foods are very similar in IDDM and NIDDM patients.

Adult↗
PubMed2006

A novel analytical method for assessing glucose variability: using CGMS in type 1 diabetes mellitus.

BACKGROUND: Marked blood glucose (BG) fluctuations may increase the risk of some complications associated with diabetes. Acute BG excursions are common in patients with diabetes, but are not usually quantified, nor can they be captured by glycosylated hemoglobin level. This study evaluated the sensitivity of novel analytical methods for assessing BG variability using CGMS (Medtronic Minimed, Northridge, CA) data from patients treated with pramlintide, a drug that acutely reduces postprandial hyperglycemia when added to insulin therapy. METHODS: Retrospective analyses were done on 24-h CGMS profiles obtained from 22 evaluable subjects with type 1 diabetes using insulin pumps and receiving preprandial three times daily injections of placebo (n = 6) or 30 microg of pramlintide (n = 16) for 4 weeks. CGMS data were recorded at baseline, after 4 weeks of treatment, and after 2 weeks off-treatment. Three parameters were calculated for each time period: variability (BG rate of change), an index for severe hypoglycemia [low BG index (LBGI)], and an index for marked hyperglycemia [high BG index (HBGI)]. RESULTS: The mean postprandial BG rate of change was significantly lower after 4 weeks of pramlintide treatment compared with placebo treatment (0.87 vs. 1.21 mg/dL/min, P < 0.01) without changes in average glycemia, illustrating the sensitivity of this parameter to medication effects. The HBGI and LBGI indicated a decreased risk of hyperglycemia without a significant increase in risk of hypoglycemia after 4 weeks of pramlintide. CONCLUSIONS: These results suggest the potential utility of several novel methods for assessing variability and glycemic extremes to gauge the effects of pharmacological interventions not captured by glycosylated hemoglobin.

Adult↗
PubMed2001

Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture.

To explore the effect of fluctuating glucose on endothelial cells, human umbilical vein endothelial cells were incubated for 14 days in media containing different glucose concentrations: 5 mmol/l, 20 mmol/l, or a daily alternating 5 or 20 mmol/l glucose. Apoptosis was studied by different methods: viability assay, cell cycle analysis, DNA fragmentation, and morphological analysis. Furthermore, the levels of Bcl-2 and Bax, well known proteins involved in apoptosis, were evaluated. Stable high glucose induced apoptosis in human umbilical vein endothelial cells, a phenomenon accompanied by a significant decrease of Bcl-2 and a simultaneous increase of Bax expression. However, apoptosis was enhanced in human umbilical vein endothelial cells exposed to intermittent, rather than constant, high glucose concentration. In this condition, Bcl-2 was not detectable, whereas Bax expression was significantly enhanced. These findings suggest that variability in glycemic control could be more deleterious to endothelial cells than a constant high concentration of glucose.

Apoptosis↗
PubMedDate not supplied

Tomando Control: a culturally appropriate diabetes education program for Spanish-speaking individuals with type 2 diabetes mellitus--evaluation of a pilot project.

PURPOSE: The purpose of this study was to pilot test the feasibility, acceptability, and efficacy of a culturally appropriate and culturally relevant Spanish-language cognitive-behavioral diabetes self-care educational intervention for Hispanic Americans with type 2 diabetes mellitus. METHODS: The study site was an urban community health center in the Northeast, at which 16 Latino patients with type 2 diabetes mellitus were recruited. This was a 1-group pretest-posttest pilot study, during which qualitative and quantitative data were collected on demographic, physiologic (HbA1c, body mass index, lipids), psychosocial (diabetes-related distress and health beliefs), knowledge, and language-based acculturation variables at baseline, 3 months, and 6 months. Data were collected using questionnaires, laboratory data, and chart review. The intervention was culturally appropriate in terms of language, social emphasis, nutritional guidance, and acknowledgment of cultural health beliefs. Descriptive and inferential statistical analysis was used to evaluate response variables of glycemic control, lipid levels, and psychosocial and knowledge outcomes. The intervention acceptability process was evaluated by attendance and attrition. RESULTS: This pilot study demonstrated excellent acceptance for and feasibility of this intervention. Most study participants (9 women, 7 men) were middle-aged married individuals who had had diabetes mellitus for an average of 8 years; English was a second language for all of them. Most were overweight and had suboptimal glycemic control and lipid profiles and moderate levels of knowledge at the outset of the study. Most had received a one-on-one diabetes educational session prior to the intervention. Over the 6 months of the study, most of both men and women showed an increase in knowledge scores, improvement in lipid profiles, and reduction in HbA1c levels. Men demonstrated a temporary increase in emotional distress much greater than that reported by women during the first 3 months of the study. CONCLUSIONS: The findings suggest that a culturally relevant type 2 diabetes mellitus educational program, particularly one that addresses different learning needs and styles of men and women, can have a positive impact on Hispanic Americans with diabetes. Implications for practice include awareness of gender-based differences in response to self-management education, the importance of providing realistic samples of meals prepared in a manner consistent with American Diabetes Association principles, and the rationale for offering a brief and focused refresher course 6 to 9 months following this type of intervention.

Adolescent↗
PubMed2005

Spotlight on insulin detemir in type 1 and 2 diabetes mellitus.

Insulin detemir (Levemir) is a soluble long-acting human insulin analog acylated with a 14-carbon fatty acid. The fatty acid modification allows insulin detemir to reversibly bind to albumin, thereby providing slow absorption and a prolonged and consistent metabolic effect of up to 24 hours in patients with type 1 or type 2 diabetes mellitus. Insulin detemir has a more predictable, protracted, and consistent effect on blood glucose than neutral protamine Hagedorn (NPH) insulin, with less intrapatient variability in glycemic control than NPH insulin or insulin glargine. Insulin detemir, administered once or twice daily, is at least as effective as NPH insulin in maintaining overall glycemic control, with a similar or lower risk of hypoglycemia, especially nocturnal hypoglycemia, compared with NPH insulin in patients with type 1 or type 2 diabetes. Insulin detemir also provides the added clinical benefit of no appreciable bodyweight gain in patients with type 1 diabetes and less bodyweight gain than NPH insulin in patients with type 2 diabetes. Insulin detemir is, therefore, a promising new option for basal insulin therapy in patients with type 1 or 2 diabetes.

Adolescent↗
PubMed1992

Alterations in glucose metabolism during menstrual cycle in women with IDDM.

OBJECTIVE: To examine the hormonal mechanisms underlying the variability in glycemic control during the different phases of the menstrual cycle in women with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Hyperglycemic (11.7 +/- 0.1 mM), hyperinsulinemic (24 +/- 3 mU/L) clamp studies were performed in 16 women with IDDM during the follicular (day 8 +/- 1) and luteal (day 23 +/- 1) phases of the menstrual cycle. Seven of the patients (group 1) experienced worsening glucose control during the luteal phase, whereas nine patients (group 2) did not. RESULTS: In group 1, glucose metabolism fell from 30.2 +/- 3.8 mumol.kg-1.min-1 during the follicular phase to 24.5 +/- 2.0 mumol.kg-1.min-1 during the luteal phase (P = 0.09), whereas in group 2 it increased from 18.5 +/- 1.2 to 23.2 +/- 2.3 mumol.kg-1.min-1 (P = 0.03). The decrease in glucose metabolism during the luteal phase in patients in group 1 was associated with a significant rise in the serum estradiol levels from the follicular to luteal phase (164 +/- 39 vs. 352 +/- 59 pM, P = 0.006), whereas this rise was not observed in group 2 (334 +/- 156 vs. 423 +/- 74 pM, NS). Changes in other reproductive hormones (progesterone, testosterone, dihydrotestosterone, androstenedione, luteinizing hormone, follicular-stimulating hormone, or prolactin) were not related to the differences in glucose uptake in the two groups. CONCLUSIONS: 1) Marked heterogeneity in glucose metabolism is seen throughout the menstrual cycle in women with IDDM, 2) a subgroup of patients exhibits worsening premenstrual hyperglycemia and a decline in insulin sensitivity during the luteal phase, and 3) the deterioration in glucose uptake in this subgroup was associated with a greater increment in estradiol levels from the follicular to the luteal phase.

Adult↗
PubMed2004

Magnesium intake and risk of type 2 diabetes in men and women.

OBJECTIVE: To examine the association between magnesium intake and risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: We followed 85,060 women and 42,872 men who had no history of diabetes, cardiovascular disease, or cancer at baseline. Magnesium intake was evaluated using a validated food frequency questionnaire every 2-4 years. After 18 years of follow-up in women and 12 years in men, we documented 4,085 and 1,333 incident cases of type 2 diabetes, respectively. RESULTS: After adjusting for age, BMI, physical activity, family history of diabetes, smoking, alcohol consumption, and history of hypertension and hypercholesterolemia at baseline, the relative risk (RR) of type 2 diabetes was 0.66 (95% CI 0.60-0.73; P for trend <0.001) in women and 0.67 (0.56-0.80; P for trend <0.001) in men, comparing the highest with the lowest quintile of total magnesium intake. The RRs remained significant after additional adjustment for dietary variables, including glycemic load, polyunsaturated fat, trans fat, cereal fiber, and processed meat in the multivariate models. The inverse association persisted in subgroup analyses according to BMI, physical activity, and family history of diabetes. CONCLUSIONS: Our findings suggest a significant inverse association between magnesium intake and diabetes risk. This study supports the dietary recommendation to increase consumption of major food sources of magnesium, such as whole grains, nuts, and green leafy vegetables.

Adult↗
PubMed1997

High variability of glycated hemoglobin concentrations in patients with IDDM followed over 9 years. What is the best index of long-term glycemic control?

OBJECTIVE: To determine variability of long-term glycemic control in patients with IDDM. RESEARCH DESIGN AND METHODS: A retrospective analysis of HbA1 among 122 IDDM patients followed over 9 years. RESULTS: Annual group mean HbA1 ranged from 8.4 to 9.3% with large standard deviations (1.7-2.0%), indicating marked variability among individuals. Fluctuations of more than +/- 1% HbA1 occurred in 50% of the patients year to year, and over 9 years the minimum-maximum range was > 3 and > 5% HbA1 in 55 and 11% of patients, respectively. In any one year, 22-43% of patients had HbA1 < 8%, but over 9 years only 3.3% were consistently < 8%. Groups divided according to baseline HbA1 of < 8, 8-10, and > 10% were significantly separated over 9 years by frequency distribution analysis of individual mean HbA1 but were indistinguishable when analyzed by individual HbA1 interquartile range (measure of variability). CONCLUSIONS: High variability of long-term glycemic control is a marked feature of IDDM, the extent of which may be relevant to microvascular risk.

Adult↗
PubMed1990

Variables associated with weight loss and improvements in glycemic control in type II diabetic patients in behavioral weight control programs.

Because weight loss is difficult to achieve, it would be helpful to determine whether there are subgroups of obese type II diabetic patients who benefit most from participation in a behavioral weight loss program. We studied 178 obese patients with type II diabetes, who participated in a 12-20 week behavioral weight loss program and were followed for 1 year after the program to determine whether age, gender, percent overweight, medication, duration of diabetes or fasting glucose were related to weight loss and/or to the magnitude of improvement in glycemic control experienced with weight loss. Gender was the only variable related to weight loss; males lost more weight and had greater decreases in percent overweight than females. The variable most strongly related to improvement in glycemic control was pretreatment fasting glucose level; patients with higher initial glucose levels experienced the greatest improvements in control. There was no evidence to support the belief that patients on insulin have poorer weight losses or that patients with long-duration diabetes benefit less from weight reduction than those with recent-onset diabetes.

Behavior Therapy↗
PubMedDate not supplied

Should minimal blood glucose variability become the gold standard of glycemic control?

The Diabetes Complications and Control Trial (DCCT) established glycosylated hemoglobin (A1C) as the gold standard of glycemic control, with levels </=7% deemed appropriate for reducing the risk of vascular complications. Yet, even when A1Cs were comparable between intensively treated subjects and their conventionally treated counterparts, the latter group experienced a markedly higher risk of progression to retinopathy over time. Our speculative explanation, based on the discovery that hyperglycemia-induced oxidative stress is the chief underlying mechanism of glucose-mediated vascular damage, was that glycemic excursions were of greater frequency and magnitude among conventionally treated patients, who received fewer insulin injections. Subsequent studies correlating the magnitude of oxidative stress with fluctuating levels of glycemia support the hypothesis that glucose variability, considered in combination with A1C, may be a more reliable indicator of blood glucose control and the risk for long-term complications than mean A1C alone.

Blood Glucose↗