Knowledge, Attitudes, and Needs: Assessing the COVID-19 Impact in Rural America.

OBJECTIVE: There is a lack of information concerning the impact of COVID-19 on rural populations. This report shares key results from a cross-sectional survey of South Dakota residents' perceptions on the impact and knowledge of COVID-19 during the early phases of the pandemic. METHODS: From March 24 to April 14, 2020, South Dakota residents (n = 4,761) reported on their psychological symptoms, pandemic-related stressful experiences, top concerns regarding the pandemic, attitudes towards COVID-19, and social distancing behaviors, and where residents were getting COVID information and who they trust to provide accurate information. RESULTS: Most participants were engaging in at least some social distancing and indicated at least moderate concern about COVID-19. Across age groups, getting sick from the coronavirus was the most frequently endorsed concern. Younger adults endorsed concerns about not being able to work, whereas older adults endorsed concerns about accessing medical care. The majority of the sample reported anxiety, worry, and sleep problems; about half the sample reported depressed mood, anhedonia, and appetite problems. Results highlight the importance of engaging public health experts and physicians in COVID-19 health messaging campaigns. CONCLUSIONS: These data provide insight into the specific challenges experienced by adults and youth in a rural state during the early phase of the pandemic. Public Health professionals and medical doctors are in a unique position to guide targeted interventions and health messaging.

Dose accuracy and injection force of disposable pens delivering pramlintide for the treatment of diabetes.

BACKGROUND: The pen injection format, typically used for insulin administration, has been adapted for the injectable, noninsulin diabetes therapy pramlintide. Administered before major meals, pramlintide therapy requires two to four injections/day in addition to the patients' usual insulin injections. The dose accuracy and injection force was determined for the 60 and 120 µg pramlintide pens. METHODS: Dose accuracy testing was conducted at two sites on multiple 60 µg (15, 30, and 60 µg doses) and 120 µg pens (60 and 120 µg doses) at prespecified temperatures (5-40 °C) and humidities (0-75%) using 29 G half-inch needles. All pens were stabilized under testing conditions for 4 h prior to testing. One site used a compression load cell (Zwick device) to test pens; one site performed tests manually. Injection-force testing was conducted at one site on multiple 60 and 120 µg pens at multiple temperatures (18-28 °C) and humidities (25-75%) using 29 and 31 G half-inch needles and an injection speed of 150 m/min. Injection-force testing was performed using a Zwick device. RESULTS: Dose accuracy for all pens tested, regardless of location, reproducibly met/exceeded acceptance criteria. Mean percentage of dose accuracy was 96.04 to 102.45% [standard deviations (SDs) 0.3 to 1.4 µg] for the 60 µg pen and 98.16 to 101.83% (SDs 0.4 to 2.5 µg) for the 120 µg pen. The average injection force across both pens did not exceed 7 N regardless of needle size. CONCLUSIONS: High dose accuracy and low injection force were observed for the 60 and 120 µg pens under a variety of conditions.

A double-blind, placebo-controlled trial assessing pramlintide treatment in the setting of intensive insulin therapy in type 1 diabetes.

OBJECTIVE: To assess safety, efficacy, and tolerability of pramlintide dose escalation with proactive mealtime insulin reduction, followed by insulin optimization, in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: This 29-week, double-blind, placebo-controlled study randomized 296 patients to pramlintide or placebo as an adjunct to insulin. During initiation, pramlintide was escalated from 15 to 60 microg/meal (15-microg increments) with recommended reductions (30-50%) in mealtime insulin. Insulin was subsequently adjusted to optimize glycemic control. End points included safety and change in HbA1c (A1C), postprandial glucose, insulin, weight, and tolerability. RESULTS: Baseline A1C was 8.1% for both groups and at week 29 had decreased comparably (pramlintide -0.5% [95% CI -0.61 to -0.33]; placebo -0.5% [-0.63 to -0.35]). Pramlintide treatment significantly reduced postprandial glucose excursions (incremental area under the curve [AUC](0-3h): pramlintide -175 +/- 40, placebo -64 +/- 38 mg x h(-1) x dl(-1); P < 0.0005) and weight (pramlintide -1.3 +/- 0.30, placebo +1.2 +/- 0.30 kg; P < 0.0001). At week 29, insulin dose decreased by 28 and 4% in pramlintide- and placebo-treated groups, respectively. Nausea, reported by 63 and 36% of patients in pramlintide and placebo groups (P < 0.01), respectively, was predominately mild to moderate in intensity. Severe hypoglycemia rates were low in both groups (pramlintide 0.57 +/- 0.09, placebo 0.30 +/- 0.06 event rate/patient-year; P < 0.05), with increased rates observed in patients remaining at 30 microg pramlintide. CONCLUSIONS: Pramlintide dose escalation with reduced mealtime insulin was effective during therapy initiation in patients with type 1 diabetes. While both groups experienced equivalent A1C reductions relative to placebo, pramlintide-treated patients experienced reductions in postprandial glucose excursions and weight, not achievable with insulin therapy alone.

Properties of pramlintide and insulin upon mixing.

PURPOSE: The pharmacokinetics, pharmacodynamics, and safety of pramlintide and various insulin formulations in patients with type 1 diabetes mellitus (DM) when given as separate injections or mixed in the same syringe before injection were studied. METHODS: In two randomized, open-label, placebo-controlled, five-period-crossover studies, patients with type 1 DM received preprandial injections of pramlintide, short-acting insulin, and long-acting insulin administered either by separate injections or after mixing in various combinations. Serum free insulin and plasma glucose concentrations were measured for 10 hours and plasma pramlintide concentrations for 5 hours after injection. RESULTS: Blood samples were collected from a total of 51 patients. All treatments involving mixtures were comparable to separate injections with respect to the area under the concentration-versus-time curve (AUC) and the maximum concentration (Cmax) of serum free insulin. There were some minor differences in the AUC and Cmax of pramlintide. No injection-site reactions or other unexpected adverse events were observed. CONCLUSION: Mixing pramlintide with short- or long-acting insulin in the same syringe before subcutaneous injection did not affect the pharmacodynamics of glucose or the pharmacokinetics of insulin or pramlintide in a clinically significant manner.

Effect of pramlintide on symptom, catecholamine, and glucagon responses to hypoglycemia in healthy subjects.

Pramlintide is an analog of the human glucoregulatory hormone amylin. Previous studies have shown no clear evidence that pramlintide modifies the response to insulin-induced hypoglycemia; however, a detailed assessment of responses at hypoglycemic thresholds has not been conducted. To further test the effect of pramlintide on symptom, catecholamine, and glucagon responses, a 3-step hypoglycemic clamp was investigated in healthy volunteers. In a randomized, double-blind, placebo-controlled, crossover study, 18 healthy subjects without diabetes received subcutaneous premeal injections of either placebo or 60 microg pramlintide 3 times daily for 5 consecutive days. On day 6, subjects received study drug with breakfast and, after a 7-hour fast, were connected to a Biostator for a 3-step, 3-hour clamp experiment (insulin infusion rate: 1.0 mU/kg/min; blood glucose targets: 70, 55, and 45 mg/dL). An intravenous (IV) infusion of pramlintide (16 microg/h) or placebo was initiated at t = 60 minutes. At the end of each 60-minute clamp step, autonomic (sweating, palpitations, hunger, etc) and neuroglycopenic (confusion, headache, odd behavior, etc) symptoms were assessed using a validated visual analog scale questionnaire. Blood samples were collected at 30-minute intervals for measurement of plasma glucose, insulin, pramlintide, catecholamine, and glucagon concentrations. Intraindividual and group mean responses showed that autonomic symptoms and plasma catecholamine and glucagon concentrations increased progressively during the clamp, with no discernible differences between pramlintide and placebo treatments. Group means for catecholamines at 60 minutes were: epinephrine 233 +/- 42, 892 +/- 85, 2,340 +/- 302 and 202 +/- 25, 774 +/- 114, 2,751 +/- 404 pg/mL and norepinephrine 1,138 +/- 86, 1,236 +/- 77, 1,721 +/- 158 and 1,278 +/- 108, 1,259 +/- 109, 1,580 +/-136 pg/mL (+/- SEM) for placebo- and pramlintide-treated groups at 70, 55, and 45 mg/dL glucose, respectively. Group means for glucagon were 72 +/- 6.3, 98 +/- 11.1, 130 +/- 14.7 and 63 +/- 3.6, 92 +/- 9.4, 120 +/- 16.0 pmol/L (+/- SEM) for placebo- and pramlintide-treated groups at 70, 55, and 45 mg/dL glucose, respectively. These results showed that pramlintide did not impair the symptom, catecholamine, and glucagon responses to insulin-induced hypoglycemia in healthy subjects.

Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial.

OBJECTIVE: Mealtime amylin replacement with the human amylin analog pramlintide, as an adjunct to mealtime insulin replacement, reduces postprandial glucose excursions in patients with type 2 diabetes. The aim of the present study was to assess the long-term efficacy and safety of pramlintide in this patient population. RESEARCH DESIGN AND METHODS: In a 52-week, double-blind, placebo-controlled, parallel-group, multicenter study, 656 patients with type 2 diabetes (age 57 +/- 10 years, diabetes duration 12 +/- 7 years, BMI 34.0 +/- 7.0 kg/m(2), HbA(1c) 9.1 +/- 1.2%, mean +/- SD) treated with insulin (alone or in combination with sulfonylureas and/or metformin) were randomized to receive additional preprandial subcutaneous injections of either placebo or pramlintide (60 micro g TID, 90 microg BID, or 120 microg BID). RESULTS: Treatment with pramlintide 120 micro g BID led to a sustained reduction from baseline in HbA(1c) (-0.68 and -0.62% at weeks 26 and 52, respectively), which was significantly greater than that seen with placebo (P < 0.05). The proportion of patients achieving an HbA(1c) <8% was approximately twofold greater with pramlintide (120 microg BID) than with placebo (46 vs. 28%, P < 0.05). The glycemic improvement with pramlintide 120 micro g BID was accompanied by a mean weight loss (-1.4 kg vs. +0.7 kg with placebo at week 52, P < 0.05) and occurred without an overall increase in the severe hypoglycemia event rate. The most common adverse event associated with pramlintide use was transient, mild-to-moderate nausea. CONCLUSIONS: Mealtime amylin replacement with pramlintide 120 microg BID, as an adjunct to insulin therapy, improves long-term glycemic and weight control in patients with type 2 diabetes.

Impact of pramlintide on glucose fluctuations and postprandial glucose, glucagon, and triglyceride excursions among patients with type 1 diabetes intensively treated with insulin pumps.

OBJECTIVE: To assess the effects of adjunctive treatment with pramlintide, an analog of the beta-cell hormone amylin, on 24-h glucose fluctuations and postprandial glucose, glucagon, and triglyceride excursions in patients with type 1 diabetes intensively treated with continuous subcutaneous insulin infusion (CSII). RESEARCH DESIGN AND METHODS: In this study, 18 patients (16 of whom could be evaluated) with type 1 diabetes (age 44 +/- 11 years, HbA(1c) 8.2 +/- 1.3% [mean +/- SD]) were given mealtime injections of 30 micro g pramlintide t.i.d. for 4 weeks in addition to their preexisting CSII regimen (16 lispro, 2 regular insulin). Mealtime insulin boluses were reduced by a minimum of 10% during the first 3 days, and re-adjusted thereafter based on clinical judgment. At weeks 0 (baseline), 4 (on treatment), and 6 (2 weeks off treatment), 24-h interstitial glucose concentrations were measured using a continuous glucose monitoring system (CGMS), and postprandial plasma glucose, glucagon, and triglyceride concentrations were measured in response to a standardized test meal. RESULTS: At baseline, patients had excessive 24-h glucose fluctuations, with 59% of the CGMS measurements >140 mg/dl, 13% <80 mg/dl, and only 28% in the euglycemic range (80-140 mg/dl). After 4 weeks on pramlintide, measurements in the hyperglycemic range declined to 48% and measurements within the euglycemic range increased to 37%. This shift from the hyperglycemic to the euglycemic range occurred with a concomitant 17% reduction in mealtime insulin dosages and without relevant increases in measurements below the euglycemic range (15%) or any severe hypoglycemic events. After 4 weeks on pramlintide, postprandial glucose, glucagon, and triglyceride excursions were reduced by approximately 86, approximately 87, and approximately 72%, respectively (incremental areas under the curve, all P < 0.05 vs. baseline). At week 6 (off treatment), the 24-h glucose profile and postprandial glucose, glucagon, and triglyceride excursions approached pretreatment values. CONCLUSIONS: In this study, the addition of pramlintide to insulin therapy reduced excessive 24-h glucose fluctuations as well as postprandial glucose, glucagon, and triglyceride excursions in patients with type 1 diabetes intensively treated with insulin pumps.